Segluromet

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions.

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 2.5 mg/850 mg film-coated tablets
Segluromet 2.5 mg/1,000 mg film-coated tablets
Segluromet 7.5 mg/850 mg film-coated tablets
Segluromet 7.5 mg/1,000 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Segluromet 2.5 mg/850 mg film-coated tablets
Each tablet contains 2.5 mg ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 850 mg of 
metformin hydrochloride.

Segluromet 2.5 mg/1,000 mg film-coated tablets
Each tablet contains 2.5 mg ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 1,000 mg of 
metformin hydrochloride.

Segluromet 7.5 mg/850 mg film-coated tablets
Each tablet contains 7.5 mg ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 850 mg metformin 
hydrochloride.
Segluromet 7.5 mg/1,000 mg film-coated tablets
Each tablet contains 7.5 mg ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 1,000 mg 
metformin hydrochloride.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet).

Segluromet 2.5 mg/850 mg film-coated tablets
Beige, 18 x 10 mm oval, film-coated tablet debossed with “2.5/850” on one side and plain on the other 
side.

Segluromet 2.5 mg/1,000 mg film-coated tablets
Pink, 19.1 x 10.6 mm oval, film-coated tablet debossed with “2.5/1000” on one side and plain on the 
other side.

Segluromet 7.5 mg/850 mg film-coated tablets
Dark brown, 18 x 10 mm oval, film-coated tablet debossed with “7.5/850” on one side and plain on 
the other side.

Segluromet 7.5 mg/1,000 mg film-coated tablets
Red, 19.1 x 10.6 mm oval, film-coated tablet debossed with “7.5/1000” on one side and plain on the 
other side.

 



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4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Segluromet is indicated in adults aged 18 years and older with type 2 diabetes mellitus as an adjunct to 
diet and exercise to improve glycaemic control:

• in patients not adequately controlled on their maximally tolerated dose of metformin alone

• in patients on their maximally tolerated doses of metformin in addition to other medicinal 
products for the treatment of diabetes

• in patients already being treated with the combination of ertugliflozin and metformin as separate 
tablets.

(For study results with respect to combinations and effects on glycaemic control, see sections 4.4, 4.5 
and 5.1.)

4.2 Posology and method of administration

Posology
The recommended dose is one tablet twice daily. The dosage should be individualised on the basis of 
the patient’s current regimen, effectiveness, and tolerability using the recommended daily dose of 
5 mg or 15 mg of ertugliflozin, while not exceeding the maximum recommended daily dose of 
metformin.

In patients with volume depletion, correcting this condition prior to initiation of Segluromet is 
recommended (see section 4.4).

If a dose is missed, it should be taken as soon as the patient remembers. Patients should not take two 
doses of Segluromet at the same time.

Adults with normal renal function (glomerular filtration rate [GFR] ≥ 90 ml/min)

For patients inadequately controlled on metformin monotherapy or metformin in combination with 
other glucose-lowering medicinal products, including insulin 
The recommended starting dose of Segluromet should provide ertugliflozin 2.5 mg twice daily (5 mg 
daily dose) and the dose of metformin similar to the dose already being taken. In patients tolerating a 
total daily dose of ertugliflozin 5 mg, the dose can be increased to a total daily dose of ertugliflozin 
15 mg if additional glycaemic control is needed. 

For patients switching from separate tablets of ertugliflozin and metformin
Patients switching from separate tablets of ertugliflozin (5 mg or 15 mg total daily dose) and 
metformin to Segluromet should receive the same daily dose of ertugliflozin and metformin already 
being taken or the nearest therapeutically appropriate dose of metformin.

When Segluromet is used in combination with insulin or an insulin secretagogue, a lower dose of 
insulin or the insulin secretagogue may be required to reduce the risk of hypoglycaemia (see 
sections 4.4, 4.5, and 4.8).

Special populations

Renal impairment
A GFR should be assessed before initiation of treatment with metformin-containing products and at 
least annually thereafter. In patients at increased risk of further progression of renal impairment and in 
the elderly, renal function should be assessed more frequently, e.g., every 3-6 months.

 



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Initiation of this medicinal product is not recommended in patients with a GFR less than 60 ml/min
(see section 4.4).

The maximum daily dose of metformin should preferably be divided into 2-3 daily doses. Factors that 
may increase the risk of lactic acidosis (see section 4.4) should be reviewed before considering 
initiation of metformin in patients with GFR < 60 ml/min. 

If no adequate strength of Segluromet is available, individual monocomponents should be used instead 
of the fixed-dose combination.

GFR ml/min Metformin Ertugliflozin

60-89 Maximum daily dose is 3,000 mg.
Dose reduction may be considered in 
relation to declining renal function.

Maximum daily dose is 15 mg.

45-59 Maximum daily dose is 2,000 mg.
The starting dose is at most half of the 
maximum dose.

Initiation is not recommended in 
patients with a glomerular 
filtration rate less than 60 ml/min
(see section 4.4).

Discontinue when GFR is 
persistently less than 45 ml/min.

30-44 Maximum daily dose is 1,000 mg.
The starting dose is at most half of the 
maximum dose.

Not recommended.

< 30 Metformin is contraindicated. Not recommended.

Hepatic impairment
Segluromet is contraindicated in patients with hepatic impairment (see sections 4.3 and 4.4).

Elderly (≥ 65 years old)
Elderly patients are more likely to have decreased renal function. Because renal function abnormalities 
can occur after initiating ertugliflozin, and metformin is known to be substantially excreted by the 
kidneys, Segluromet should be used with caution in the elderly. Regular assessment of renal function 
is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in elderly 
patients (see section 4.4). Renal function and risk of volume depletion should be taken into account 
(see sections 4.4 and 4.8).
There is limited experience with Segluromet in patients ≥ 75 years of age.

Paediatric population
The safety and efficacy of Segluromet in children under 18 years of age have not been established. No 
data are available.

Method of administration
Segluromet should be taken orally twice daily with meals to reduce the gastrointestinal adverse 
reactions associated with metformin. In case of swallowing difficulties, the tablet could be broken or 
crushed as it is an immediate-release dosage form.

4.3 Contraindications

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1;
- any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis [DKA]);
- diabetic pre coma;

 



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- severe renal failure (GFR less than 30 ml/min), end-stage renal disease (ESRD), or patients on 
dialysis (see section 4.4);

- acute condition with the potential to alter renal function, such as:
- dehydration,
- severe infection,
- shock;

- acute or chronic disease that may cause tissue hypoxia, such as:
- cardiac or respiratory failure,
- recent myocardial infarction,
- shock;

- hepatic impairment;
- acute alcohol intoxication, alcoholism.

4.4 Special warnings and precautions for use

General
Segluromet should not be used in patients with type 1 diabetes mellitus.

Lactic acidosis
Lactic acidosis, a very rare but serious metabolic complication, most often occurs at acute worsening 
of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute 
worsening of renal function and increases the risk of lactic acidosis. 

In case of dehydration (severe vomiting, diarrhoea, fever or reduced fluid intake), metformin should be 
temporarily discontinued and contact with a health care professional is recommended.

Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and 
non-steroidal anti-inflammatory drugs [NSAIDs]) should be initiated with caution in metformin-
treated patients. Other risk factors for lactic acidosis are excessive alcohol intake, hepatic 
insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting and any conditions 
associated with hypoxia, as well as concomitant use of medicinal products that may cause lactic 
acidosis (see sections 4.3 and 4.5).

Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is 
characterised by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia 
followed by coma. In case of suspected symptoms, the patient should stop taking metformin and seek 
immediate medical attention. Diagnostic laboratory findings are decreased blood pH (< 7.35), 
increased plasma lactate levels (> 5 mmol/l) and an increased anion gap and lactate/pyruvate ratio.

Administration of iodinated contrast agents
Intravascular administration of iodinated contrast agents may lead to contrast-induced nephropathy, 
resulting in metformin accumulation and an increased risk of lactic acidosis. Segluromet should be 
discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours 
after, provided that renal function has been re-evaluated and found to be stable (see sections 4.2 and 
4.5).

Renal function
The efficacy of ertugliflozin is dependent on renal function, and efficacy is reduced in patients who 
have moderate renal impairment and likely absent in patients with severe renal impairment (see 
section 4.2).

Segluromet should not be initiated in patients with a GFR below 60 ml/min. Segluromet should be 
discontinued when GFR is persistently below 45 ml/min due to a reduction of efficacy. 

GFR should be assessed before treatment initiation and regularly thereafter (see section 4.2). More 
frequent renal function monitoring is recommended in patients with a GFR below 60 ml/min. 

 



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Metformin is contraindicated in patients with GFR < 30 ml/min and should be temporarily 
discontinued in the presence of conditions that alter renal function (see section 4.3).

Surgery
Segluromet must be discontinued at the time of surgery under general, spinal, or epidural anaesthesia. 
Therapy may be restarted no earlier than 48 hours following surgery or resumption of oral nutrition 
and provided that renal function has been re-evaluated and found to be stable.

Hypotension/Volume depletion
Ertugliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction. 
Therefore, symptomatic hypotension may occur after initiating Segluromet (see section 4.8),
particularly in patients with impaired renal function (eGFR less than 60 ml/min/1.73 m2 or a CrCl less 
than 60 ml/min), elderly patients (≥ 65 years), patients on diuretics, or patients on anti-hypertensive 
therapy with a history of hypotension. Before initiating Segluromet, volume status should be assessed 
and corrected if indicated. Monitor for signs and symptoms after initiating therapy.

Due to its mechanism of action, ertugliflozin induces an osmotic diuresis and increases serum 
creatinine and decreases eGFR. Increases in serum creatinine and decreases in eGFR were greater in 
patients with moderate renal impairment (see section 4.8).

In case of conditions that may lead to fluid loss (e.g., gastrointestinal illness), careful monitoring of 
volume status (e.g., physical examination, blood pressure measurements, laboratory tests including 
haematocrit) and electrolytes is recommended for patients receiving ertugliflozin. Temporary 
interruption of treatment with Segluromet should be considered until the fluid loss is corrected.

Diabetic ketoacidosis
Rare cases of DKA, including life-threatening and fatal cases, have been reported in clinical trials and 
post-marketing in patients treated with sodium glucose co-transporter-2 (SGLT2) inhibitors, and cases 
have been reported in clinical trials with ertugliflozin. In a number of cases, the presentation of the 
condition was atypical with only moderately increased blood glucose values, below 14 mmol/l 
(250 mg/dl). It is not known if DKA is more likely to occur with higher doses of ertugliflozin.

The risk of diabetic ketoacidosis must be considered in the event of non-specific symptoms such as 
nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual 
fatigue, or sleepiness. Patients should be assessed for ketoacidosis immediately if these symptoms 
occur, regardless of blood glucose level.

In patients where DKA is suspected or diagnosed, treatment with Segluromet should be discontinued 
immediately.

Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute 
serious medical illnesses. Monitoring of ketones is recommended in these patients. Measurement of 
blood ketone levels is preferred to urine. Treatment with Segluromet may be restarted when the ketone 
values are normal and the patient’s condition has stabilised.

Before initiating Segluromet, factors in the patient history that may predispose to ketoacidosis should 
be considered.

Patients who may be at higher risk of DKA include patients with a low beta-cell function reserve (e.g., 
type 2 diabetes patients with low C-peptide or latent autoimmune diabetes in adults (LADA) or
patients with a history of pancreatitis), patients with conditions that lead to restricted food intake or 
severe dehydration, patients for whom insulin doses are reduced and patients with increased insulin 
requirements due to acute medical illness, surgery, or alcohol abuse. SGLT2 inhibitors should be used 
with caution in these patients.

Restarting SGLT2 inhibitor treatment in patients with previous DKA while on SGLT2 inhibitor 
treatment is not recommended, unless another clear precipitating factor is identified and resolved.

 



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The safety and efficacy of Segluromet in patients with type 1 diabetes have not been established and 
Segluromet should not be used for treatment of patients with type 1 diabetes. Limited data from 
clinical trials suggest that DKA occurs with common frequency when patients with type 1 diabetes are 
treated with SGLT2 inhibitors.

Lower limb amputations 
In an ongoing clinical study of ertugliflozin added to existing therapy in type 2 diabetes patients with a 
history of established cardiovascular disease, an approximately 1.2-1.6-fold increase in cases of lower 
limb amputation (primarily of the toe) has been observed in patients treated with ertugliflozin. An 
increase in cases of lower limb amputation (primarily of the toe) has also been observed in long-term 
clinical studies with another SGLT2 inhibitor. As an underlying mechanism has not been established, 
risk factors, apart from general risk factors, for amputation are unknown.

Before initiating ertugliflozin/metformin, consider factors in the patient history that may increase the 
risk for amputation. As precautionary measures, consideration should be given to carefully monitoring 
patients with a higher risk for amputation events and counselling patients about the importance of 
routine preventative foot care and maintaining adequate hydration. Consideration may also be given to 
stopping treatment with ertugliflozin/metformin in patients who develop events which may precede 
amputation such as lower-extremity skin ulcer, infection, osteomyelitis or gangrene.

Hypoglycaemia with concomitant use of insulin and insulin secretagogues
Ertugliflozin may increase the risk of hypoglycaemia when used in combination with insulin and/or an 
insulin secretagogue, which are known to cause hypoglycaemia (see section 4.8). Therefore, a lower 
dose of insulin or insulin secretagogue may be required to minimise the risk of hypoglycaemia when 
used in combination with Segluromet (see sections 4.2 and 4.5).

Genital mycotic infections
Ertugliflozin increases the risk of genital mycotic infections. In trials with SGLT2 inhibitors, patients 
with a history of genital mycotic infections and uncircumcised males were more likely to develop 
genital mycotic infections (see section 4.8). Patients should be monitored and treated appropriately.

Urinary tract infections
Urinary glucose excretion may be associated with an increased risk of urinary tract infections.
The incidence of urinary tract infections was not notably different in the ertugliflozin 5 mg and 15 mg 
groups (4.0% and 4.1%) and the placebo group (3.9%). Most of the events were mild or moderate and 
no serious case was reported. Temporary interruption of ertugliflozin should be considered when 
treating pyelonephritis or urosepsis.

Necrotising fasciitis of the perineum (Fournier’s gangrene) 
Post-marketing cases of necrotising fasciitis of the perineum, (also known as Fournier’s gangrene), 
have been reported in female and male patients taking SGLT2 inhibitors. This is a rare but serious and 
potentially life-threatening event that requires urgent surgical intervention and antibiotic treatment. 

Patients should be advised to seek medical attention if they experience a combination of symptoms of 
pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Be aware 
that either uro-genital infection or perineal abscess may precede necrotising fasciitis. If Fournier’s 
gangrene is suspected, Segluromet should be discontinued and prompt treatment (including antibiotics 
and surgical debridement) should be instituted. 

Elderly patients
Elderly patients may be at an increased risk of volume depletion. Patients 65 years and older treated 
with ertugliflozin had a higher incidence of adverse reactions related to volume depletion compared to 
younger patients. The risk of metformin-associated lactic acidosis increases with the patient’s age 
because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment than 
younger patients. Segluromet is expected to have diminished efficacy in elderly patients with renal 
impairment (see sections 4.2 and 4.8). Assess renal function more frequently in elderly patients. 

 



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Cardiac failure 
Experience in New York Heart Association (NYHA) class I-II is limited, and there is no experience in 
clinical studies with ertugliflozin in NYHA class III-IV.

Urine laboratory assessments
Due to the mechanism of action of ertugliflozin, patients taking Segluromet will test positive for 
glucose in their urine. Alternative methods should be used to monitor glycaemic control.

Interference with 1,5 anhydroglucitol (1,5-AG) assay
Monitoring glycaemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are 
unreliable in assessing glycaemic control in patients taking medicines containing an SGLT2 inhibitor. 
Alternative methods should be used to monitor glycaemic control.

Sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

Pharmacokinetic drug interaction studies with Segluromet have not been performed; however, such 
studies have been conducted with ertugliflozin and metformin, the individual active substances of 
Segluromet.

Ertugliflozin

Pharmacodynamic interactions

Diuretics
Ertugliflozin may add to the diuretic effect of diuretics and may increase the risk of dehydration and 
hypotension (see section 4.4).

Insulin and insulin secretagogues
Insulin and insulin secretagogues, such as sulphonylureas, cause hypoglycaemia. Ertugliflozin may 
increase the risk of hypoglycaemia when used in combination with insulin and/or an insulin 
secretagogue. Therefore, a lower dose of insulin or an insulin secretagogue may be required to reduce 
the risk of hypoglycaemia when used in combination with Segluromet (see sections 4.2, 4.4, and 4.8). 

Pharmacokinetic interactions

Effects of other medicinal products on the pharmacokinetics of ertugliflozin
Metabolism by UGT1A9 and UGT2B7 is the primary clearance mechanism for ertugliflozin. 

Interaction studies conducted in healthy subjects, using a single dose design, suggest that the 
pharmacokinetics of ertugliflozin are not altered by sitagliptin, metformin, glimepiride, or simvastatin.

Multiple-dose administration of rifampin (a UGT and CYP inducer) decreases ertugliflozin AUC and 
Cmax by 39% and 15%, respectively. This decrease in exposure is not considered clinically relevant and 
therefore, no dose adjustment is recommended. A clinically relevant effect with other inducers (e.g., 
carbamazepine, phenytoin, phenobarbital) is not expected. 

The impact of UGT inhibitors on the pharmacokinetics of ertugliflozin has not been studied clinically, 
but potential increase in ertugliflozin exposure due to UGT inhibition is not considered to be clinically 
relevant.

 



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Effects of ertugliflozin on the pharmacokinetics of other medicinal products
Interaction studies conducted in healthy volunteers suggest that ertugliflozin had no clinically relevant 
effect on the pharmacokinetics of sitagliptin, metformin, and glimepiride.

Coadministration of simvastatin with ertugliflozin resulted in a 24% and 19% increase in AUC and 
Cmax of simvastatin, respectively, and 30% and 16% increase in AUC and Cmax of simvastatin acid, 
respectively. The mechanism for the small increases in simvastatin and simvastatin acid is unknown 
and is not perpetrated through OATP inhibition by ertugliflozin. These increases are not considered to 
be clinically meaningful.

Metformin

Concomitant use not recommended

Alcohol
Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in cases of 
fasting, malnutrition or hepatic impairment.

Iodinated contrast agents
Segluromet must be discontinued prior to or at the time of the imaging procedure and not restarted 
until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable 
(see sections 4.2 and 4.4).

Combinations requiring precautions for use
Some medicinal products can adversely affect renal function, which may increase the risk of lactic 
acidosis, e.g., NSAIDs, including selective cyclo-oxygenase (COX) II inhibitors, 
angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists and diuretics, 
especially loop diuretics. When starting or using such products in combination with metformin, close 
monitoring of renal function is necessary.

Organic cation transporters (OCT)
Metformin is a substrate of both transporters OCT1 and OCT2.

Coadministration of metformin with 
 Inhibitors of OCT1 (such as verapamil) may reduce efficacy of metformin. 
 Inducers of OCT1 (such as rifampicin) may increase gastrointestinal absorption and efficacy of 

metformin.
 Inhibitors of OCT2 (such as cimetidine, dolutegravir, ranolazine, trimethoprime, vandetanib, 

isavuconazole) may decrease the renal elimination of metformin and thus lead to an increase in 
metformin plasma concentration.

 Inhibitors of both OCT1 and OCT2 (such as crizotinib, olaparib) may alter efficacy and renal 
elimination of metformin.

Caution is therefore advised, especially in patients with renal impairment, when these drugs are 
coadministered with metformin, as metformin plasma concentration may increase. If needed, dose 
adjustment of metformin may be considered as OCT inhibitors/inducers may alter the efficacy of 
metformin.

Glucocorticoids (given by systemic and local routes), beta 2 agonists, and diuretics have intrinsic 
hyperglycaemic activity. The patient should be informed and more frequent blood glucose monitoring 
performed, especially at the beginning of treatment with such medicinal products. If necessary, the 
dose of the antihyperglycaemic medicinal product should be adjusted during therapy with the other 
medicinal product and on its discontinuation.

 



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4.6 Fertility, pregnancy and lactation

Pregnancy
There are no data from the use of Segluromet in pregnant women. 

A limited amount of data suggests the use of metformin in pregnant women is not associated with an 
increased risk of congenital malformations. Animal studies with metformin do not indicate harmful 
effects with respect to pregnancy, embryonic or foetal development, parturition or post-natal 
development (see section 5.3).

There are limited data from the use of ertugliflozin in pregnant women. Based on results from animal 
studies, ertugliflozin may affect renal development and maturation (see section 5.3). Therefore, 
Segluromet should not be used during pregnancy. 

Breast-feeding
There is no information regarding the presence of ertugliflozin in human milk, the effects on the 
breast-fed infant, or the effects on milk production. Metformin is present in human breast milk.
Ertugliflozin and metformin are present in the milk of lactating rats. Ertugliflozin caused effects in the
offspring of lactating rats.

Pharmacologically mediated effects were observed in juvenile rats treated with ertugliflozin (see
section 5.3). Since human kidney maturation occurs in utero and during the first 2 years of life when 
exposure from breast-feeding may occur, a risk to newborns/infants cannot be excluded. Segluromet 
should not be used during breast-feeding.

Fertility
The effect of Segluromet on fertility in humans has not been studied. No effects of ertugliflozin or 
metformin on fertility were observed in animal studies (see section 5.3).

4.7 Effects on ability to drive and use machines

Segluromet has no or negligible influence on the ability to drive and use machines. Patients should be 
alerted to the risk of hypoglycaemia when Segluromet is used in combination with insulin or an insulin 
secretagogue and to the elevated risk of adverse reactions related to volume depletion, such as postural 
dizziness (see sections 4.2, 4.4, and 4.8). 

4.8 Undesirable effects

Summary of the safety profile

Ertugliflozin and Metformin
The safety of concomitantly administered ertugliflozin and metformin has been evaluated in 
1,083 patients with type 2 diabetes mellitus treated for 26 weeks in a pool of two placebo-controlled 
trials: as ertugliflozin add on therapy to metformin and as ertugliflozin add-on therapy to sitagliptin 
and metformin (see section 5.1). The incidence and type of adverse reactions in these two trials were 
similar to the adverse reactions seen with ertugliflozin. There were no additional adverse reactions 
identified in the pooling of these two placebo-controlled trials that included metformin relative to the 
three placebo-controlled studies with ertugliflozin (see below).

Ertugliflozin

Pool of placebo-controlled trials
The primary assessment of safety was conducted in a pool of three 26-week, placebo-controlled trials. 
Ertugliflozin was used as monotherapy in one trial and as add-on therapy in two trials (see 
section 5.1). These data reflect exposure of 1,029 patients to ertugliflozin with a mean exposure 
duration of approximately 25 weeks. Patients received ertugliflozin 5 mg (N=519), ertugliflozin 15 mg 
(N=510), or placebo (N=515) once daily.

 



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The most commonly reported adverse reactions across the clinical program were vulvovaginal mycotic 
infection, and other female genital mycotic infections. Serious diabetic ketoacidosis occurred rarely. 
See “Description of selected adverse reactions” for frequencies and see section 4.4.

Tabulated list of adverse reactions
Adverse reactions listed below are classified according to frequency and system organ class (SOC). 
Frequency categories are defined according to the following convention: very common (≥ 1/10), 
common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very 
rare (< 1/10,000), not known (cannot be estimated from the available data).

Table 1: Adverse reactions 

System Organ Class
Frequency

Adverse Reaction

Infections and infestations

Very common

Common

Not known

Vulvovaginal mycotic infection and other female genital 
mycotic infections*,†,1

Balanitis candida and other male genital mycotic 
infections*,†,1

Necrotising fasciitis of the perineum (Fournier’s gangrene)*

Metabolism and nutrition disorders

Common

Rare

Very rare

Hypoglycaemia*,†,1

Diabetic ketoacidosis*,†,1

Lactic acidosis*,2, Vitamin B12 deficiency
‡,2

Nervous system disorders
Common Taste disturbance2

Vascular disorders
Common Volume depletion*,†,1

Gastrointestinal disorders
Very common Gastrointestinal symptoms§,2

Hepatobiliary disorders
Very rare Liver function test abnormal2, Hepatitis2

Skin and subcutaneous tissue disorders
Very rare Erythema2, Pruritus2, Urticaria2

Renal and urinary disorders
Common

Uncommon

Increased urination¶,1

Dysuria1, Blood creatinine increased/Glomerular filtration 
rate decreased†,1

Reproductive system and breast disorders
Common Vulvovaginal pruritus1

General disorders and administration site conditions
Common Thirst#,1

Investigations
Common Serum lipids changedÞ,1, Haemoglobin increasedß,1, BUN 

increasedà,1
1 Adverse reaction with ertugliflozin.
2 Adverse reaction with metformin.
* See Section 4.4.
† See subsections below for additional information.
‡ Long-term treatment with metformin has been associated with a decrease in vitamin B12 absorption, which may very 

rarely result in clinically significant vitamin B12 deficiency (e.g., megaloblastic anaemia).

 



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§ Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite occur most 
frequently during initiation of therapy and resolve spontaneously in most cases.

¶
Includes: pollakiuria, micturition urgency, polyuria, urine output increased, and nocturia.

#
Includes: thirst and polydipsia.

Þ Mean percent changes from baseline for ertugliflozin 5 mg and 15 mg versus placebo, respectively, were LDL-C 5.8% 
and 8.4% versus 3.2%; total cholesterol 2.8% and 5.7% versus 1.1%; however, HDL-C 6.2% and 7.6% versus 1.9%.
Median percent changes from baseline for ertugliflozin 5 mg and 15 mg versus placebo, respectively, were
triglycerides -3.9% and -1.7% versus 4.5%.

ß The proportion of subjects having at least 1 increase in haemoglobin > 2.0 g/dL was higher in the ertugliflozin 5 mg and 
15 mg groups (4.7% and 4.1%, respectively) compared to the placebo group (0.6%).

à The proportion of subjects having any occurrence of BUN values ≥ 50% increase and value >ULN was numerically 
higher in the ertugliflozin 5 mg group and higher in the 15 mg group (7.9% and 9.8%, respectively) relative to the 
placebo group (5.1%).

Description of selected adverse reactions

Volume depletion (ertugliflozin)
Ertugliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction and 
adverse reactions related to volume depletion. In the pool of placebo-controlled studies, the incidence 
of adverse events related to volume depletion (dehydration, dizziness postural, presyncope, syncope, 
hypotension, and orthostatic hypotension) was low (< 2%) and not notably different across the 
ertugliflozin and placebo groups. In the subgroup analyses in the broader pool of Phase 3 studies, 
subjects with eGFR < 60 mL/min/1.73 m2, subjects ≥ 65 years of age and subjects on diuretics had a 
higher incidence of volume depletion in the ertugliflozin groups relative to the comparator group (see 
sections 4.2 and 4.4). In subjects with eGFR < 60 mL/min/1.73 m2, the incidence was 5.1%, 2.6%, and 
0.5% for ertugliflozin 5 mg, ertugliflozin 15 mg, and the comparator group and for subjects with 
eGFR 45 to < 60 mL/min/1.73 m2, the incidence was 6.4%, 3.7%, and 0% respectively.

Hypoglycaemia (ertugliflozin)
In the pool of placebo-controlled studies, the incidence of documented hypoglycaemia was increased 
for ertugliflozin 5 mg and 15 mg (5.0% and 4.5%) compared to placebo (2.9%). In this population, the 
incidence of severe hypoglycaemia was 0.4% in each group. When ertugliflozin was used as 
monotherapy, the incidence of hypoglycaemic events in the ertugliflozin groups was 2.6% in both 
groups and 0.7% in the placebo group. When used as add-on to metformin, the incidence of 
hypoglycaemic events was 7.2% in the ertugliflozin 5 mg group, 7.8% in the ertugliflozin 15 mg 
group and 4.3% in the placebo group.

When ertugliflozin was added to metformin and compared to sulphonylurea, the incidence of 
hypoglycaemia was higher for the sulphonylurea (27%) compared to ertugliflozin (5.6% and 8.2% for 
ertugliflozin 5 mg and 15 mg, respectively). 

In patients with moderate renal impairment taking insulins, SU, or meglitinides as background 
medication, documented hypoglycaemia was 36%, 27% and 36% for ertugliflozin 5 mg, ertugliflozin 
15 mg, and placebo, respectively (see sections 4.2, 4.4, and 4.5).

Diabetic ketoacidosis (ertugliflozin)
Across the clinical program for ertugliflozin, ketoacidosis was identified in 3 of 3,409 (0.1%) 
ertugliflozin-treated patients and 0.0% of comparator-treated patients (see section 4.4).

Blood creatinine increased/Glomerular filtration rate decreased and renal-related events
(ertugliflozin)
Initial increases in mean creatinine and decreases in mean eGFR in patients treated with ertugliflozin 
were generally transient during continuous treatment. Patients with moderate renal impairment at 
baseline had larger mean changes that did not return to baseline at Week 26; these changes reversed
after treatment discontinuation.

Renal-related adverse reactions (e.g., acute kidney injury, renal impairment, acute prerenal failure) 
may occur in patients treated with ertugliflozin, particularly in patients with moderate renal 

 



13

impairment where the incidence of renal-related adverse reactions was 2.5%, 1.3%, and 0.6% in 
patients treated with ertugliflozin 5 mg, ertugliflozin 15 mg, and placebo, respectively.

Genital mycotic infections (ertugliflozin)
In the pool of three placebo-controlled clinical trials, female genital mycotic infections (e.g., genital 
candidiasis, genital infection fungal, vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal 
mycotic infection, vulvovaginitis) occurred in 9.1%, 12%, and 3.0% of females treated with 
ertugliflozin 5 mg, ertugliflozin 15 mg, and placebo, respectively. In females, discontinuation due to 
genital mycotic infections occurred in 0.6% and 0% of patients treated with ertugliflozin and placebo, 
respectively (see section 4.4).

In the same pool, male genital mycotic infections (e.g., balanitis candida, balanoposthitis, genital 
infection, genital infection fungal) occurred in 3.7%, 4.2%, and 0.4% of males treated with 
ertugliflozin 5 mg, ertugliflozin 15 mg, and placebo, respectively. Male genital mycotic infections 
occurred more commonly in uncircumcised males. In males, discontinuations due to genital mycotic 
infections occurred in 0.2% and 0% of patients treated with ertugliflozin and placebo, respectively. In 
rare instances, phimosis was reported and sometimes circumcision was performed (see section 4.4).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

In the event of an overdose with Segluromet, employ the usual supportive measures (e.g., remove 
unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute 
supportive treatment) as dictated by the patient’s clinical status.

Ertugliflozin
Ertugliflozin did not show any toxicity in healthy subjects at single oral doses up to 300 mg and 
multiple doses up to 100 mg daily for 2 weeks. No potential acute symptoms and signs of overdose 
were identified. Removal of ertugliflozin by haemodialysis has not been studied.

Metformin
Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 g. 
Hypoglycaemia was reported in approximately 10% of cases, but no causal association with 
metformin hydrochloride has been established. Lactic acidosis has been reported in approximately 
32% of metformin overdose cases (see section 4.4). Lactic acidosis is a medical emergency and must 
be treated in a hospital. Metformin is dialyzable with a clearance of up to 170 ml/min under good 
haemodynamic conditions. Therefore, haemodialysis may be useful for removal of accumulated drug 
from patients in whom metformin overdose is suspected.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in diabetes, combinations of oral blood glucose lowering 
drugs, ATC code: A10BD23.

Mechanism of action
Segluromet combines two antihyperglycaemic agents with complementary mechanisms of action to 
improve glycaemic control in patients with type 2 diabetes: ertugliflozin, a SGLT2 inhibitor, and 
metformin hydrochloride, a member of the biguanide class.

 

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14

Ertugliflozin
SGLT2 is the predominant transporter responsible for reabsorption of glucose from the glomerular 
filtrate back into the circulation. Ertugliflozin is a potent, selective, and reversible inhibitor of SGLT2. 
By inhibiting SGLT2, ertugliflozin reduces renal reabsorption of filtered glucose and lowers the renal 
threshold for glucose, and thereby increases urinary glucose excretion.

Metformin
Metformin is an antihyperglycaemic agent which improves glucose tolerance in patients with type 2 
diabetes, lowering both basal and post-prandial plasma glucose. Its pharmacologic mechanisms of 
action are different from other classes of oral antihyperglycaemic agents. Metformin decreases hepatic 
glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by 
increasing peripheral glucose uptake and utilisation. Unlike sulphonylureas, metformin does not 
produce hypoglycaemia in either patients with type 2 diabetes or normal subjects, except in special 
circumstances (see section 4.5), and does not cause hyperinsulinaemia. With metformin therapy, 
insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response 
may actually decrease.

Pharmacodynamic effects

Ertugliflozin

Urinary glucose excretion and urinary volume
Dose-dependent increases in the amount of glucose excreted in urine were observed in healthy 
subjects and in patients with type 2 diabetes mellitus following single- and multiple-dose 
administration of ertugliflozin. Dose-response modelling indicates that ertugliflozin 5 mg and 15 mg 
result in near maximal urinary glucose excretion (UGE) in patients with type 2 diabetes mellitus, 
providing 87% and 96% of maximal inhibition, respectively.

Clinical efficacy and safety

Ertugliflozin in combination with metformin
The efficacy and safety of ertugliflozin in combination with metformin have been studied in 
4 multi-centre, randomised, double-blind, placebo- and active comparator-controlled, Phase 3 clinical 
studies involving 3,643 patients with type 2 diabetes. Across the four studies, the racial distribution 
ranged from 66.2% to 80.3% White, 10.6% to 20.3% Asian, 1.9% to 10.3% Black, and 4.5% to 7.4% 
other. Hispanic or Latino patients comprised 15.6% to 34.5% of the population. The mean age of the 
patients across these four studies ranged from 55.1 to 59.1 years (range 21 years to 86 years); 15.6% to 
29.9% of patients were ≥65 years of age and 0.6% to 3.8% were ≥75 years of age.

Ertugliflozin as add-on combination therapy with metformin
A total of 621 patients with type 2 diabetes inadequately controlled on metformin monotherapy 
(≥ 1,500 mg/day) participated in a randomised, double-blind, multi-centre, 26-week, placebo-
controlled study to evaluate the efficacy and safety of ertugliflozin in combination with metformin. 
Patients were randomised to ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo administered once 
daily in addition to continuation of background metformin therapy (see Table 2).

 



15

Table 2: Results at Week 26 from a placebo-controlled study for ertugliflozin used in 
combination with metformin*

Ertugliflozin 5 mg Ertugliflozin 15 mg Placebo

HbA1c (%) N = 207 N = 205 N = 209

Baseline (mean) 8.1 8.1 8.2

Change from baseline (LS mean†) -0.7 -0.9 -0.0

Difference from placebo (LS mean†, 95% CI) -0.7‡ (-0.9, -0.5) -0.9‡ (-1.1, -0.7)

Patients [N (%)] with HbA1c < 7% 73 (35.3)§ 82 (40.0)§ 33 (15.8)

Body Weight (kg) N = 207 N = 205 N = 209

Baseline (mean) 84.9 85.3 84.5

Change from baseline (LS mean†) -3.0 -2.9 -1.3

Difference from placebo (LS mean†, 95% CI) -1.7‡ (-2.2, -1.1) -1.6‡ (-2.2, -1.0)

* N includes all randomised, treated patients who had at least one measurement of the outcome variable.
† Least squares means adjusted for treatment, time, prior antihyperglycaemic medication (metformin monotherapy or 

metformin + another AHA), baseline eGFR (continuous), menopausal status randomisation stratum (men, premenopausal 
women, women who are perimenopausal or < 3 years postmenopausal, women who are  3 years postmenopausal) and the 
interaction of time by treatment.

‡ p 0.001 compared to placebo.
§ p< 0.001 compared to placebo (based on adjusted odds ratio comparisons from a logistic regression model using multiple

imputation for missing data values).

Factorial study with ertugliflozin and sitagliptin as add-on combination therapy with metformin
A total of 1,233 patients with type 2 diabetes participated in a randomised, double-blind, multi-centre, 
26-week, active-controlled study to evaluate the efficacy and safety of ertugliflozin 5 mg or 15 mg in 
combination with sitagliptin 100 mg compared to the individual components. Patients with type 2 
diabetes inadequately controlled on metformin monotherapy (≥ 1,500 mg/day) were randomised to one 
of five active-treatment arms: ertugliflozin 5 mg or 15 mg, sitagliptin 100 mg, or sitagliptin 100 mg in 
combination with 5 mg or 15 mg ertugliflozin administered once daily in addition to continuation of 
background metformin therapy (see Table 3).

 



16

Table 3: Results at Week 26 from a factorial study with ertugliflozin and sitagliptin as add-on 
combination therapy with metformin compared to individual components alone*

Ertugliflozin 
5 mg

Ertugliflozin 
15 mg

Sitagliptin 
100 mg

Ertugliflozin 5 mg +
Sitagliptin 100 mg

Ertugliflozin 15 mg 
+ Sitagliptin 100 mg

HbA1c (%) N = 250 N = 248 N = 247 N = 243 N = 244

Baseline (mean) 8.6 8.6 8.5 8.6 8.6

Change from baseline (LS mean†) -1.0 -1.1 -1.1 -1.5 -1.5

Difference from

Sitagliptin 

Ertugliflozin 5 mg

-0.4‡ (-0.6, -0.3)

-0.5‡ (-0.6, -0.3)

-0.5‡ (-0.6, -0.3)

Ertugliflozin 15 mg

(LS mean†, 95% CI)

-0.4‡ (-0.6, -0.3)

Patients [N (%)] with HbA1c < 7% 66 (26.4) 79 (31.9) 81 (32.8) 127§ (52.3) 120§ (49.2)

Body Weight (kg) N = 250 N = 248 N = 247 N = 243 N = 244

Baseline (mean) 88.6 88.0 89.8 89.5 87.5

Change from baseline (LS mean†) -2.7 -3.7 -0.7 -2.5 -2.9

Difference from Sitagliptin

(LS mean†, 95% CI)

-1.8‡ (-2.5, -1.2) -2.3‡ (-2.9, -1.6)

* N includes all randomised, treated patients who had at least one measurement of the outcome variable.
† Least squares means adjusted for treatment, time, baseline eGFR and the interaction of time by treatment.
‡ p< 0.001 compared to control group.
§ p< 0.001 compared to corresponding dose of ertugliflozin or sitagliptin (based on adjusted odds ratio comparisons from a logistic

regression model using multiple imputation for missing data values).

Ertugliflozin as add-on combination therapy with metformin and sitagliptin
A total of 463 patients with type 2 diabetes inadequately controlled on metformin (≥ 1,500 mg/day) 
and sitagliptin 100 mg once daily participated in a randomised, double-blind, multi-centre, 26-week, 
placebo-controlled study to evaluate the efficacy and safety of ertugliflozin. Patients were randomised 
to ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo administered once daily in addition to 
continuation of background metformin and sitagliptin therapy (see Table 4).

Table 4: Results at Week 26 from an add-on study of ertugliflozin in combination with 
metformin and sitagliptin*

Ertugliflozin 5 mg Ertugliflozin 15 mg Placebo

HbA1c (%) N = 156 N = 153 N = 153

Baseline (mean) 8.1 8.0 8.0

Change from baseline (LS mean†) -0.8 -0.9 -0.1

Difference from placebo (LS mean†, 95% CI) -0.7‡ (-0.9, -0.5) -0.8‡ (-0.9, -0.6)

Patients [N (%)] with HbA1c < 7% 50 (32.1)‡ 61 (39.9)‡ 26 (17.0)

Body Weight (kg) N = 156 N = 153 N = 153

Baseline (mean) 87.6 86.6 86.5

Change from baseline (LS mean†) -3.3 -3.0 -1.3

Difference from placebo (LS mean†, 95% CI) -2.0‡ (-2.6, -1.4) -1.7‡ (-2.3, -1.1)
* N includes all randomised, treated patients who had at least one measurement of the outcome variable.
† Least squares means adjusted for treatment, time, prior antihyperglycaemic medication.
‡ p 0.001 compared to placebo.

 



17

Active-controlled study of ertugliflozin versus glimepiride as add-on combination therapy with 
metformin 
A total of 1,326 patients with type 2 diabetes inadequately controlled on metformin monotherapy 
participated in a randomised, double-blind, multi-centre, 52-week, active comparator-controlled study 
to evaluate the efficacy and safety of ertugliflozin in combination with metformin. These patients, who 
were receiving metformin monotherapy (≥ 1,500 mg/day), were randomised to ertugliflozin 5 mg, 
ertugliflozin 15 mg, or glimepiride administered once daily in addition to continuation of background 
metformin therapy. Glimepiride was initiated at 1 mg/day and titrated up to a maximum dose of 6 or 
8 mg/day (depending on maximum approved dose in each country) or a maximum tolerated dose or 
down-titrated to avoid or manage hypoglycaemia. The mean daily dose of glimepiride was 3.0 mg (see 
Table 5).

Table 5: Results at Week 52 from an active-controlled study comparing ertugliflozin to 
glimepiride as add-on therapy in patients inadequately controlled on metformin*

Ertugliflozin 5 mg Ertugliflozin 15 mg Glimepiride

HbA1c (%) N = 448 N = 440 N = 437

Baseline (mean) 7.8 7.8 7.8

Change from baseline (LS mean†) -0.6 -0.6 -0.7

Difference from glimepiride (LS mean†, 95% CI) 0.2 (0.1, 0.3) 0.1‡ (-0.0, 0.2)

Patients [N (%)] with HbA1c < 7% 154 (34.4) 167 (38.0) 190 (43.5)

Body Weight (kg) N = 448 N = 440 N = 437

Baseline (mean) 87.9 85.6 86.8

Change from baseline (LS mean†) -3.0 -3.4 0.9

Difference from glimepiride (LS mean†, 95% CI) -3.9 (-4.4, -3.4) -4.3§ (-4.8, -3.8)

* N includes all randomised, treated patients who had at least one measurement of the outcome variable.
† Least squares means adjusted for treatment, time, prior antihyperglycaemic medication (monotherapy or dual therapy), 

baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.
‡ Non-inferiority is declared when the upper bound of the two-sided 95% confidence interval (CI) for the mean difference is 

less than 0.3%.
§ p< 0.001 compared to glimepiride.

Fasting plasma glucose
In three placebo-controlled studies, ertugliflozin resulted in statistically significant reductions in FPG. 
For ertugliflozin 5 mg and 15 mg, respectively, the placebo-corrected reductions in FPG were 1.92 and 
2.44 mmol/l as monotherapy, 1.48 and 2.12 mmol/l as add-on to metformin, and 1.40 and 1.74 mmol/l 
as add-on to metformin and sitagliptin. 

The combination of ertugliflozin and sitagliptin on a background of metformin resulted in significantly 
greater reductions in FPG compared to sitagliptin or ertugliflozin alone. The combination of 
ertugliflozin 5 or 15 mg and sitagliptin resulted in incremental FPG reductions of 0.46 and
0.65 mmol/l compared to the ertugliflozin alone or 1.02 and 1.28 mmol/l compared to sitagliptin 
alone, respectively.

Efficacy in patients with baseline HbA1c ≥ 9% 
In the study of ertugliflozin in combination with metformin in patients with baseline HbA1c from 
7.0-10.5%, the placebo-corrected reductions in HbA1c for the subgroup of patients in the study with 
baseline HbA1c ≥ 9% were 1.31% and 1.43% with ertugliflozin 5 mg and 15 mg, respectively.

In the study of patients inadequately controlled on metformin with baseline HbA1c from 7.5-11.0%, 
among the subgroup of patients with a baseline HbA1c ≥ 10%, the combination of ertugliflozin 5 mg 
or 15 mg with sitagliptin resulted in reductions of HbA1c of 2.35% and 2.66%, respectively, compared 
to 2.10%, 1.30%, and 1.82% for ertugliflozin 5 mg, ertugliflozin 15 mg, and sitagliptin alone, 
respectively.

 



18

Blood pressure
As add-on to metformin, ertugliflozin 5 mg and 15 mg resulted in statistically significant
placebo-corrected reductions in SBP of 3.7 mmHg and 4.5 mmHg, respectively. As add-on to 
metformin and sitagliptin, ertugliflozin 5 mg and 15 mg resulted in statistically significant
placebo-corrected reductions in SBP of 2.9 mmHg and 3.9 mmHg, respectively. 

In a 52-week, active-controlled study versus glimepiride, reductions from baseline in SBP were 
2.2 mmHg and 3.8 mmHg for ertugliflozin 5 mg and 15 mg, respectively, while subjects treated with 
glimepiride had an increase in SBP from baseline of 1.0 mmHg.

Subgroup analysis
In patients with type 2 diabetes treated with ertugliflozin in combination with metformin, clinically 
meaningful reductions in HbA1c were observed in subgroups defined by age, sex, race, ethnicity, 
geographic region, baseline BMI, baseline HbA1c, and duration of type 2 diabetes mellitus.

Paediatric population 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Segluromet in all subsets of the paediatric population in the treatment of type 2 diabetes (see 
section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

Segluromet
Segluromet has been shown to be bioequivalent to coadministration of corresponding doses of 
ertugliflozin and metformin tablets.

Ertugliflozin

General introduction
The pharmacokinetics of ertugliflozin are similar in healthy subjects and patients with type 2 diabetes. 
The steady state mean plasma AUC and Cmax were 398 ng∙hr/ml and 81 ng/ml, respectively, with 5 mg 
ertugliflozin once daily treatment, and 1,193 ng∙hr/ml and 268 ng/ml, respectively, with 15 mg 
ertugliflozin once daily treatment. Steady-state is reached after 4 to 6 days of once-daily dosing with 
ertugliflozin. Ertugliflozin does not exhibit time-dependent pharmacokinetics and accumulates in 
plasma up to 10-40% following multiple dosing.

Absorption
Following single-dose oral administration of 5 mg and 15 mg of ertugliflozin, peak plasma 
concentrations (median Tmax) of ertugliflozin occur at 1 hour post-dose under fasted conditions. 
Plasma Cmax and AUC of ertugliflozin increase in a dose-proportional manner following single doses 
from 0.5 mg to 300 mg and following multiple doses from 1 mg to 100 mg. The absolute oral 
bioavailability of ertugliflozin following administration of a 15-mg dose is approximately 100%. 

Administration of ertugliflozin with a high-fat and high-calorie meal decreases ertugliflozin Cmax by 
29% and prolongs Tmax by 1 hour, but does not alter AUC as compared with the fasted state. The 
observed effect of food on ertugliflozin pharmacokinetics is not considered clinically relevant, and 
ertugliflozin may be administered with or without food. In Phase 3 clinical trials, ertugliflozin was 
administered without regard to meals.

The effects of a high-fat meal on the pharmacokinetics of ertugliflozin and metformin when 
administered as Segluromet tablets are comparable to those reported for the individual tablets. Food 
had no meaningful effect on AUCinf of ertugliflozin or metformin, but reduced mean ertugliflozin Cmax
by approximately 41% and metformin Cmax by approximately 29% compared to the fasted condition.

Ertugliflozin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) 
transporters.

 



19

Distribution
The mean steady-state volume of distribution of ertugliflozin following an intravenous dose is 86 l. 
Plasma protein binding of ertugliflozin is 93.6% and is independent of ertugliflozin plasma 
concentrations. Plasma protein binding is not meaningfully altered in patients with renal or hepatic 
impairment. The blood-to-plasma concentration ratio of ertugliflozin is 0.66.

Ertugliflozin is not a substrate of organic anion transporters (OAT1, OAT3), organic cation 
transporters (OCT1, OCT2), or organic anion transporting polypeptides (OATP1B1, OATP1B3) in 
vitro.

Biotransformation
Metabolism is the primary clearance mechanism for ertugliflozin. The major metabolic pathway for 
ertugliflozin is UGT1A9 and UGT2B7-mediated O-glucuronidation to two glucuronides that are 
pharmacologically inactive at clinically relevant concentrations. CYP-mediated (oxidative) 
metabolism of ertugliflozin is minimal (12%).

Elimination
The mean systemic plasma clearance following an intravenous 100 µg dose was 11 l/hr. The mean 
elimination half-life in type 2 diabetic patients with normal renal function was estimated to be 
17 hours based on the population pharmacokinetic analysis. Following administration of an oral 
[14C]-ertugliflozin solution to healthy subjects, approximately 41% and 50% of the drug-related 
radioactivity was eliminated in faeces and urine, respectively. Only 1.5% of the administered dose was 
excreted as unchanged ertugliflozin in urine and 34% as unchanged ertugliflozin in faeces, which is 
likely due to biliary excretion of glucuronide metabolites and subsequent hydrolysis to parent.

Special populations

Renal impairment
In a Phase 1 clinical pharmacology study in patients with type 2 diabetes and mild, moderate, or 
severe renal impairment (as determined by eGFR), following a single-dose administration of 15 mg 
ertugliflozin, the mean increases in AUC of ertugliflozin were ≤ 1.7-fold, compared to subjects with 
normal renal function. These increases in ertugliflozin AUC are not considered clinically relevant. 
There were no clinically meaningful differences in the ertugliflozin Cmax values among the different 
renal function groups. The 24-hour urinary glucose excretion declined with increasing severity of renal 
impairment (see section 4.4). The plasma protein binding of ertugliflozin was unaffected in patients 
with renal impairment.

Hepatic impairment
Moderate hepatic impairment (based on the Child-Pugh classification) did not result in an increase in 
exposure of ertugliflozin. The AUC of ertugliflozin decreased by approximately 13%, and Cmax
decreased by approximately 21% compared to subjects with normal hepatic function. This decrease in 
ertugliflozin exposure is not considered clinically meaningful. There is no clinical experience in 
patients with Child-Pugh class C (severe) hepatic impairment. The plasma protein binding of 
ertugliflozin was unaffected in patients with moderate hepatic impairment.

Paediatric population
No studies with ertugliflozin have been performed in paediatric patients.

Effects of age, body weight, gender and race
Based on a population pharmacokinetic analysis, age, body weight, gender, and race do not have a 
clinically meaningful effect on the pharmacokinetics of ertugliflozin.

 



20

Drug Interactions

In vitro assessment of ertugliflozin
In in vitro studies, ertugliflozin and ertugliflozin glucuronides did not inhibit or inactivate CYPs 1A2, 
2C9, 2C19, 2C8, 2B6, 2D6, or 3A4, and did not induce CYPs 1A2, 2B6, or 3A4. Ertugliflozin and 
ertugliflozin glucuronides did not inhibit the activity of UGTs 1A6, 1A9 or 2B7 in vitro. Ertugliflozin 
was a weak inhibitor of UGTs 1A1 and 1A4 in vitro at higher concentrations that are not clinically 
relevant. Ertugliflozin glucuronides had no effect on these isoforms. Overall, ertugliflozin is unlikely 
to affect the pharmacokinetics of concurrently administered drugs eliminated by these enzymes.

Ertugliflozin or ertugliflozin glucuronides do not meaningfully inhibit P-gp, OCT2, OAT1, or OAT3 
transporters or transporting polypeptides OATP1B1 and OATP1B3 at clinically relevant 
concentrations in vitro. Overall, ertugliflozin is unlikely to affect the pharmacokinetics of concurrently 
administered medications that are substrates of these transporters.

Metformin

Absorption
The absolute bioavailability of a metformin hydrochloride 500-mg tablet given under fasting 
conditions is approximately 50-60%. Studies using single oral doses of metformin hydrochloride 
tablets 500 mg to 1,500 mg, and 850 mg to 2,550 mg, indicate that there is a lack of dose 
proportionality with increasing doses, which is due to decreased absorption rather than an alteration in 
elimination. At usual clinical doses and dosing schedules of metformin hydrochloride tablets, steady-
state plasma concentrations of metformin are reached within 24-48 hours and are generally <1 µg/ml. 
During controlled clinical trials of metformin, maximum metformin plasma levels did not exceed 
5 µg/mL, even at maximum doses.

Food decreases the extent of and slightly delays the absorption of metformin, as shown by 
approximately a 40% lower mean peak plasma concentration (Cmax), a 25% lower area under the 
plasma concentration versus time curve (AUC), and a 35-minute prolongation of time to peak plasma 
concentration (Tmax) following administration of a single 850-mg tablet of metformin with food, 
compared to the same tablet strength administered fasting. The clinical relevance of these decreases is 
unknown.

Distribution
The apparent volume of distribution (V/F) of metformin following single oral doses of metformin 
hydrochloride tablets 850 mg averaged 654 ± 358 l. Metformin is negligibly bound to plasma proteins. 
Metformin partitions into erythrocytes. 

Biotransformation
Metformin is excreted unchanged in the urine. No metabolites have been identified in humans.

Elimination
Renal clearance is approximately 3.5 times greater than creatinine clearance, which indicates that 
tubular secretion is the major route of metformin elimination. Following oral administration, 
approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, 
with a plasma elimination half-life of approximately 6.2 hours.

Special populations

Renal impairment
In patients with decreased renal function, the plasma and blood half-life of metformin is prolonged and 
the renal clearance is decreased in proportion to the decrease in eGFR (see sections 4.3 and 4.4).

Hepatic impairment
No pharmacokinetic studies of metformin have been conducted in patients with hepatic insufficiency.

 



21

Effects of age, body weight, gender and race
Limited data from controlled pharmacokinetic studies of metformin in healthy elderly subjects suggest 
that total plasma clearance of metformin is decreased, the half-life is prolonged, and Cmax is increased, 
compared to healthy young subjects. From these data, it appears that the change in metformin 
pharmacokinetics with aging is primarily accounted for by a change in renal function.

Metformin pharmacokinetic parameters did not differ significantly between normal subjects and 
patients with type 2 diabetes when analysed according to gender. Similarly, in controlled clinical 
studies in patients with type 2 diabetes, the antihyperglycaemic effect of metformin was comparable in 
males and females.

No studies of metformin pharmacokinetic parameters according to race have been performed. In 
controlled clinical studies of metformin in patients with type 2 diabetes, the antihyperglycaemic effect 
was comparable in Whites (n=249), Blacks (n=51), and Hispanics (n=24).

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, acute toxicity, repeated dose toxicity, genotoxicity, and carcinogenic potential.

General toxicity

Ertugliflozin
Repeat-dose oral toxicity studies were conducted in mice, rats, and dogs for up to 13, 26, and 
39 weeks, respectively. Signs of toxicity that were considered adverse were generally observed at 
exposures greater than or equal to 77 times the human unbound exposure (AUC) at the maximum 
recommended human dose (MRHD) of 15 mg/day. Most toxicity was consistent with pharmacology 
related to urinary glucose loss and included decreased body weight and body fat, increased food 
consumption, diarrhoea, dehydration, decreased serum glucose and increases in other serum 
parameters reflective of increased protein metabolism, gluconeogenesis and electrolyte imbalances, 
and urinary changes such as polyuria, glucosuria, and calciuria. Microscopic changes related to 
glucosuria and/or calciuria observed only in rodents included dilatation of renal tubules, hypertrophy 
of zona glomerulosa in adrenal glands (rats), and increased trabecular bone (rats). Except for emesis, 
there were no adverse toxicity findings in dogs at 379 times the human unbound exposure (AUC) at 
the MRHD of 15 mg/day.

Carcinogenesis

Ertugliflozin
In the 2-year mouse carcinogenicity study, ertugliflozin was administered by oral gavage at doses of 5, 
15, and 40 mg/kg/day. There were no ertugliflozin-related neoplastic findings at doses up to 
40 mg/kg/day (approximately 41 times human unbound exposure at the MRHD of 15 mg/day based on 
AUC). In the 2-year rat carcinogenicity study, ertugliflozin was administered by oral gavage at doses 
of 1.5, 5, and 15 mg/kg/day. Ertugliflozin-related neoplastic findings included an increased incidence 
of benign adrenal medullary pheochromocytoma in male rats at 15 mg/kg/day. This finding was 
attributed to carbohydrate malabsorption leading to altered calcium homeostasis and was not 
considered relevant to human risk. The no-observed-effect level (NOEL) for neoplasia was
5 mg/kg/day (approximately 16 times human unbound exposure at the MRHD of 15 mg/day).

Metformin
Long-term carcinogenicity studies have been performed in rats (dosing duration of 104 weeks) and 
mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg/day and 1,500 mg/kg/day, 
respectively. These doses are both approximately four times the maximum recommended human daily 
dose of 2,000 mg based on body surface area comparisons. No evidence of carcinogenicity with 
metformin was found in either male or female mice. Similarly, there was no tumorigenic potential 
observed with metformin in male rats. There was, however, an increased incidence of benign stromal 
uterine polyps in female rats treated with 900 mg/kg/day.

 



22

Mutagenesis

Ertugliflozin
Ertugliflozin was not mutagenic or clastogenic with or without metabolic activation in the microbial 
reverse mutation, in vitro cytogenetic (human lymphocytes), and in vivo rat micronucleus assays.

Metformin
There was no evidence of a mutagenic potential of metformin in the following in vitro tests: Ames test 
(S. typhimurium), gene mutation test (mouse lymphoma cells), or chromosomal aberrations test 
(human lymphocytes). Results in the in vivo mouse micronucleus test were also negative.

Reproductive toxicology

Ertugliflozin
In the rat fertility and embryonic development study, male and female rats were administered 
ertugliflozin at 5, 25, and 250 mg/kg/day. No effects on fertility were observed at 250 mg/kg/day 
(approximately 386 times human unbound exposure at the MRHD of 15 mg/day based on AUC 
comparisons). Ertugliflozin did not adversely affect developmental outcomes in rats and rabbits at 
maternal exposures that were 239 and 1,069 times, respectively, the human exposure at the maximum 
clinical dose of 15 mg/day, based on AUC. At a maternally toxic dose in rats (250 mg/kg/day), lower 
foetal viability and a higher incidence of a visceral malformation were observed at maternal exposure 
that was 510 times the maximum clinical dose of 15 mg/day.

In the pre- and post-natal development study, decreased post-natal growth and development were 
observed in rats administered ertugliflozin gestation day 6 through lactation day 21 at 
≥ 100 mg/kg/day (estimated 239 times the human exposure at the maximum clinical dose of 
15 mg/day, based on AUC). Sexual maturation was delayed in both sexes at 250 mg/kg/day (estimated 
620 times the MRHD at 15 mg/day, based on AUC).

When ertugliflozin was administered to juvenile rats from post-natal day (PND) 21 to PND 90, a 
period of renal development corresponding to the late second and third trimesters of human pregnancy, 
increased kidney weights, dilatation of the renal pelvis and tubules, and renal tubular mineralization 
were seen at an exposure 13 times the maximum clinical dose of 15 mg/day, based on AUC. Effects 
on bone (shorter femur length, increased trabecular bone in the femur) as well as effects of delayed 
puberty were observed at an exposure 817 times the MHRD of 15 mg/day based on AUC. The effects 
on kidney and bone did not fully reverse after the 1-month recovery period.

Metformin
Fertility of male or female rats was unaffected by metformin when administered at doses as high as 
600 mg/kg/day, which is approximately three times the maximum recommended human daily dose 
based on body surface area comparisons. Metformin did not adversely affect developmental outcomes 
when administered to rats and rabbits at doses up to 600 mg/kg/day. This represents an exposure of 
about 2 and 6 times the exposure at the maximum recommended human dose of 2,000 mg based on 
body surface area comparisons for rats and rabbits, respectively. Determination of foetal 
concentrations demonstrated a partial placental barrier to metformin.

 



23

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core
Povidone K29-32 (E1201)
Microcrystalline cellulose (E460)
Crospovidone (E1202)
Sodium lauryl sulfate (E487)
Magnesium stearate (E470b)

Film coating 
Segluromet 2.5 mg/850 mg film-coated tablets and Segluromet 7.5 mg/850 mg film-coated tablets
Hypromellose (E464)
Hydroxypropyl cellulose (E463)
Titanium dioxide (E171)
Iron oxide red (E172)
Iron oxide yellow (E172)
Iron oxide black (E172)
Carnauba wax (E903)

Segluromet 2.5 mg/1,000 mg film-coated tablets and Segluromet 7.5 mg/1,000 mg film-coated tablets
Hypromellose (E464)
Hydroxypropyl cellulose (E463)
Titanium dioxide (E171)
Iron oxide red (E172)
Carnauba wax (E903)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container 

Alu/PVC/PA/Alu blisters.
Packs of 14, 28, 56, 60, 168, and 180 film-coated tablets in non-perforated blisters and multipacks 
containing 196 (4 packs of 49) film-coated tablets in non-perforated blisters.
Packs of 30x1 film-coated tablets in perforated unit dose blisters.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

 



24

7. MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

8. MARKETING AUTHORISATION NUMBER(S) 

Segluromet 2.5 mg/850 mg film-coated tablets
EU/1/18/1265/001
EU/1/18/1265/002
EU/1/18/1265/003
EU/1/18/1265/004
EU/1/18/1265/005
EU/1/18/1265/006
EU/1/18/1265/007
EU/1/18/1265/029

Segluromet 2.5 mg/1,000 mg film-coated tablets
EU/1/18/1265/008
EU/1/18/1265/009
EU/1/18/1265/010
EU/1/18/1265/011
EU/1/18/1265/012
EU/1/18/1265/013
EU/1/18/1265/014
EU/1/18/1265/030

Segluromet 7.5 mg/850 mg film-coated tablets
EU/1/18/1265/015
EU/1/18/1265/016
EU/1/18/1265/017
EU/1/18/1265/018
EU/1/18/1265/019
EU/1/18/1265/020
EU/1/18/1265/021
EU/1/18/1265/031

Segluromet 7.5 mg/1,000 mg film-coated tablets
EU/1/18/1265/022
EU/1/18/1265/023
EU/1/18/1265/024
EU/1/18/1265/025
EU/1/18/1265/026
EU/1/18/1265/027
EU/1/18/1265/028
EU/1/18/1265/032

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 23 March 2018

 



25

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.

 

http://www.ema.europa.eu/


26

ANNEX II

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT

 



27

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) responsible for batch release
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
Netherlands

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. The marketing authorisation 
holder (MAH) shall submit the first PSUR for this product within 6 months following authorisation.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing 
authorisation and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached. 

 



28

ANNEX III

LABELLING AND PACKAGE LEAFLET

 



29

A. LABELLING

 



30

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON FOR SEGLUROMET 2.5 mg/850 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 2.5 mg/850 mg film-coated tablets
ertugliflozin/metformin hydrochloride

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 2.5 mg of ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 850 mg of 
metformin hydrochloride.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

14 film-coated tablets
28 film-coated tablets 
30x1 film-coated tablets
56 film-coated tablets
60 film-coated tablets
168 film-coated tablets
180 film-coated tablets
Multipack: 196 (4 packs of 49) film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

 



31

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1265/001 (14 film-coated tablets)
EU/1/18/1265/002 (28 film-coated tablets)
EU/1/18/1265/003 (30x1 film-coated tablets)
EU/1/18/1265/004 (56 film-coated tablets)
EU/1/18/1265/005 (60 film-coated tablets)
EU/1/18/1265/006 (168 film-coated tablets)
EU/1/18/1265/007 (180 film-coated tablets)
EU/1/18/1265/029 (196 (4 x 49) film-coated tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Segluromet 2.5 mg/850 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

 



32

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

INTERMEDIATE CARTON WITHOUT BLUE BOX – MULTIPACKS - SEGLUROMET 
2.5 mg/850 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 2.5 mg/850 mg film-coated tablets
ertugliflozin/metformin hydrochloride

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 2.5 mg of ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 850 mg of 
metformin hydrochloride.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

49 film-coated tablets. Component of a multipack, can’t be sold separately.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

 



33

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1265/029

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Segluromet 2.5 mg/850 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

Not applicable.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

Not applicable.

 



34

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR SEGLUROMET 2.5 mg/850 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 2.5 mg/850 mg tablets
ertugliflozin/metformin hydrochloride

2. NAME OF THE MARKETING AUTHORISATION HOLDER

MSD

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

 



35

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON FOR SEGLUROMET 2.5 mg/1000 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 2.5 mg/1000 mg film-coated tablets
ertugliflozin/metformin hydrochloride

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 2.5 mg of ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 1000 mg of 
metformin hydrochloride.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

14 film-coated tablets
28 film-coated tablets 
30x1 film-coated tablets
56 film-coated tablets
60 film-coated tablets
168 film-coated tablets
180 film-coated tablets
Multipack: 196 (4 packs of 49) film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

 



36

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1265/008 (14 film-coated tablets)
EU/1/18/1265/009 (28 film-coated tablets)
EU/1/18/1265/010 (30x1 film-coated tablets)
EU/1/18/1265/011 (56 film-coated tablets)
EU/1/18/1265/012 (60 film-coated tablets)
EU/1/18/1265/013 (168 film-coated tablets)
EU/1/18/1265/014 (180 film-coated tablets)
EU/1/18/1265/030 (196 (4 x 49) film-coated tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Segluromet 2.5 mg/1000 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

 



37

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

INTERMEDIATE CARTON WITHOUT BLUE BOX - MULTIPACKS - SEGLUROMET 
2.5 mg/1000 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 2.5 mg/1000 mg film-coated tablets
ertugliflozin/metformin hydrochloride

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 2.5 mg of ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 1000 mg of 
metformin hydrochloride.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

49 film-coated tablets. Component of a multipack, can’t be sold separately.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

 



38

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1265/030

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Segluromet 2.5 mg/1000 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

Not applicable.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

Not applicable.

 



39

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR SEGLUROMET 2.5 mg/1000 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 2.5 mg/1000 mg tablets
ertugliflozin/metformin hydrochloride

2. NAME OF THE MARKETING AUTHORISATION HOLDER

MSD

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

 



40

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON FOR SEGLUROMET 7.5 mg/850 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 7.5 mg/850 mg film-coated tablets
ertugliflozin/metformin hydrochloride

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 7.5 mg of ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 850 mg of 
metformin hydrochloride.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

14 film-coated tablets
28 film-coated tablets 
30x1 film-coated tablets
56 film-coated tablets
60 film-coated tablets
168 film-coated tablets
180 film-coated tablets
Multipack: 196 (4 packs of 49) film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

 



41

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1265/015 (14 film-coated tablets)
EU/1/18/1265/016 (28 film-coated tablets)
EU/1/18/1265/017 (30x1 film-coated tablets)
EU/1/18/1265/018 (56 film-coated tablets)
EU/1/18/1265/019 (60 film-coated tablets)
EU/1/18/1265/020 (168 film-coated tablets)
EU/1/18/1265/021 (180 film-coated tablets)
EU/1/18/1265/031 (196 (4 x 49) film-coated tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Segluromet 7.5 mg/850 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC 
SN
NN

 



42

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

INTERMEDIATE CARTON WITHOUT BLUE BOX – MULTIPACKS - SEGLUROMET 
7.5 mg/850 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 7.5 mg/850 mg film-coated tablets
ertugliflozin/metformin hydrochloride

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 7.5 mg of ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 850 mg of 
metformin hydrochloride.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

49 film-coated tablets. Component of a multipack, can’t be sold separately.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

 



43

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1265/031

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Segluromet 7.5 mg/850 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

Not applicable.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

Not applicable.

 



44

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR SEGLUROMET 7.5 mg/850 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 7.5 mg/850 mg tablets
ertugliflozin/metformin hydrochloride

2. NAME OF THE MARKETING AUTHORISATION HOLDER

MSD

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

 



45

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON FOR SEGLUROMET 7.5 mg/1000 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 7.5 mg/1000 mg film-coated tablets
ertugliflozin/metformin hydrochloride

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 7.5 mg of ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 1000 mg of 
metformin hydrochloride.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

14 film-coated tablets
28 film-coated tablets 
30x1 film-coated tablets
56 film-coated tablets
60 film-coated tablets
168 film-coated tablets
180 film-coated tablets
Multipack: 196 (4 packs of 49) film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

 



46

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1265/022 (14 film-coated tablets)
EU/1/18/1265/023 (28 film-coated tablets)
EU/1/18/1265/024 (30x1 film-coated tablets)
EU/1/18/1265/025 (56 film-coated tablets)
EU/1/18/1265/026 (60 film-coated tablets)
EU/1/18/1265/027 (168 film-coated tablets)
EU/1/18/1265/028 (180 film-coated tablets)
EU/1/18/1265/032 (196 (4 x 49) film-coated tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Segluromet 7.5 mg/1000 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC 
SN
NN

 



47

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

INTERMEDIATE CARTON WITHOUT BLUE BOX – MULTIPACKS - SEGLUROMET 
7.5 mg/1000 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 7.5 mg/1000 mg film-coated tablets
ertugliflozin/metformin hydrochloride

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 7.5 mg of ertugliflozin (as ertugliflozin L-pyroglutamic acid) and 1000 mg of 
metformin hydrochloride.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

49 film-coated tablets. Component of a multipack, can’t be sold separately.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

 



48

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/18/1265/032

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Segluromet 7.5 mg/1000 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

Not applicable.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

Not applicable.

 



49

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER FOR SEGLUROMET 7.5 mg/1000 mg

1. NAME OF THE MEDICINAL PRODUCT

Segluromet 7.5 mg/1000 mg tablets
ertugliflozin/metformin hydrochloride

2. NAME OF THE MARKETING AUTHORISATION HOLDER

MSD

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

 



50

B. PACKAGE LEAFLET

 



51

Package leaflet: Information for the patient

Segluromet 2.5 mg/850 mg film-coated tablets
Segluromet 2.5 mg/1,000 mg film-coated tablets
Segluromet 7.5 mg/850 mg film-coated tablets

Segluromet 7.5 mg/1,000 mg film-coated tablets
ertugliflozin/metformin hydrochloride

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects.

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, pharmacist, or nurse.
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Segluromet is and what it is used for 
2. What you need to know before you take Segluromet
3. How to take Segluromet
4. Possible side effects
5. How to store Segluromet
6. Contents of the pack and other information

1. What Segluromet is and what it is used for

What Segluromet is
Segluromet contains two active substances, ertugliflozin and metformin.
 Ertugliflozin belongs to a group of medicines called sodium glucose co-transporter-2 (SGLT2)

inhibitors.
 Metformin belongs to a group of medicines called biguanides.

What Segluromet is used for
 Segluromet lowers blood sugar levels in adult patients (aged 18 years and older) with type 2 

diabetes.
 Segluromet can be used instead of taking both ertugliflozin and metformin as separate tablets. 
 Segluromet can be used alone or with some other medicines that lower blood sugar. 
 You need to keep following your food and exercise plan while taking Segluromet.

How Segluromet works
 Ertugliflozin works by blocking the SGLT2 protein in your kidneys. This causes blood sugar to 

be removed in your urine.
 Metformin works by inhibiting sugar (glucose) production in the liver. 

What is type 2 diabetes?
Type 2 diabetes is a condition in which your body does not make enough insulin or the insulin that 
your body produces does not work as well as it should. Your body can also make too much sugar. 
When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems,
like heart disease, kidney disease, blindness and poor circulation.

 



52

2. What you need to know before you take Segluromet

Do not take Segluromet
 if you are allergic to ertugliflozin or metformin or any of the other ingredients of this medicine 

(listed in section 6).
 if you have severely reduced kidney function or need dialysis.
 if you have uncontrolled diabetes, with, for example, severe hyperglycaemia (high blood 

glucose), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see “Risk of lactic 
acidosis” below) or ketoacidosis. Ketoacidosis is a condition in which substances called ‘ketone 
bodies’ accumulate in the blood and which can lead to diabetic pre-coma. Symptoms include 
stomach pain, fast and deep breathing, sleepiness, or your breath developing an unusual fruity 
smell.

 if you have a severe infection or are dehydrated.
 if you have recently had a heart attack or have severe circulatory problems, such as ‘shock’ or 

breathing difficulties.
 if you have liver problems.
 if you drink alcohol to excess (either regularly or from time to time).
Do not take Segluromet if any of the above apply to you. If you are not sure, talk to your doctor before 
taking Segluromet. 

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before and while taking Segluromet, if you:
 have kidney problems.
 have or have had yeast infections of the vagina or penis.
 have ever had serious heart disease or if you have had a stroke.
 have type 1 diabetes. Segluromet should not be used to treat this condition.
 take other diabetes medicines; you are more likely to get low blood sugar with certain 

medicines.
 might be at risk of dehydration (for example, if you are taking medicines that increase urine 

production [diuretics] lower blood pressure or if you are over 65 years old). Ask about ways to 
prevent dehydration.

 experience rapid weight loss, feeling sick or being sick, stomach pain, excessive thirst, fast and 
deep breathing, confusion, unusual sleepiness or tiredness, a sweet smell to your breath, a sweet 
or metallic taste in your mouth or a different odour to your urine or sweat, contact a doctor or 
the nearest hospital straight away. These symptoms could be a sign of “diabetic ketoacidosis” –
a problem you can get with diabetes because of increased levels of “ketone bodies” in your 
urine or blood, seen in tests. The risk of developing diabetic ketoacidosis may be increased with 
prolonged fasting, excessive alcohol consumption, dehydration, sudden reductions in insulin 
dose, or a higher need of insulin due to major surgery or serious illness.

 have had a lower limb amputation.

It is important to check your feet regularly and adhere to any other advice regarding foot care and 
adequate hydration given by your healthcare professional. You should notify your doctor immediately 
if you notice any wounds or discolouration, or if you experience any tenderness or pain in your feet. 
Some studies indicate that taking ertugliflozin may have contributed to an increase in cases of lower 
limb amputation (mainly of the toe).

Talk to your doctor immediately if you develop a combination of symptoms of pain, tenderness, 
redness, or swelling of the genitals or the area between the genitals and the anus with fever or feeling 
generally unwell. These symptoms could be a sign of a rare but serious or even life-threatening 
infection, called necrotising fasciitis of the perineum or Fournier’s gangrene which destroys the tissue 
under the skin. Fournier’s gangrene has to be treated immediately.

 



53

When this medicine is used in combination with insulin or medicines that increase insulin release from 
the pancreas, low blood sugar (hypoglycaemia) can occur. Your doctor may reduce the dose of your 
insulin or other medicine.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Risk of lactic acidosis
Segluromet may cause a very rare, but very serious side effect called lactic acidosis, particularly if 
your kidneys are not working properly. The risk of developing lactic acidosis is also increased with 
uncontrolled diabetes, serious infections, prolonged fasting or alcohol intake, dehydration (see further 
information below), liver problems and any medical conditions in which a part of the body has a 
reduced supply of oxygen (such as acute severe heart disease).
If any of the above apply to you, talk to your doctor for further instructions.

Stop taking Segluromet for a short time if you have a condition that may be associated with 
dehydration (significant loss of body fluids) such as severe vomiting, diarrhoea, fever, exposure to 
heat or if you drink less fluid than normal. Talk to your doctor for further instructions.

Stop taking Segluromet and contact a doctor or the nearest hospital immediately if you 
experience some of the symptoms of lactic acidosis, as this condition may lead to coma.
Symptoms of lactic acidosis include:
 vomiting
 stomach ache (abdominal pain)
 muscle cramps
 a general feeling of not being well with severe tiredness
 difficulty in breathing
 reduced body temperature and heartbeat
Lactic acidosis is a medical emergency and must be treated in a hospital.

If you need to have major surgery you must stop taking Segluromet during and for some time after the 
procedure. Your doctor will decide when you must stop and when to restart your treatment with 
Segluromet.

During treatment with Segluromet, your doctor will check your kidney function at least once a year or 
more frequently if you are elderly and/or if you have worsening kidney function.

Urine glucose
Because of how Segluromet works, your urine will test positive for sugar (glucose) while you are on 
this medicine.

Children and adolescents
Children and adolescents below 18 years should not take this medicine. It is not known if this 
medicine is safe and effective when used in children and adolescents under 18 years of age.

Other medicines and Segluromet
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 

You may need more frequent blood glucose and kidney function tests, or your doctor may need to 
adjust the dose of Segluromet. In particular, tell your doctor:
 if you are taking medicines which increase urine production (diuretics).
 if you are taking other medicines that lower the sugar in your blood, such as insulin or

medicines that increase insulin release from the pancreas.
 if you are taking medicines used to treat pain and inflammation (NSAID and COX-2-inhibitors, 

such as ibuprofen and celecoxib).

 



54

 if you are taking certain medicines for the treatment of high blood pressure (ACE inhibitors and 
angiotensin II receptor antagonists).

If any of the above apply to you (or you are not sure), tell your doctor.

If you need to have an injection of a contrast medium that contains iodine into your bloodstream, for 
example, in the context of an X-ray or scan, you must stop taking Segluromet before or at the time of 
the injection. Your doctor will decide when you must stop and when to restart your treatment with 
Segluromet.

Segluromet with alcohol
Avoid excessive alcohol intake while taking Segluromet since this may increase the risk of lactic 
acidosis (see section “Warnings and precautions”).

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine.

It is not known if Segluromet can harm your unborn baby. If you are pregnant, talk with your doctor 
about the best way to control your blood sugar while you are pregnant. You should not use Segluromet
if you are pregnant.

It is not known if Segluromet passes into breast milk. Talk with your doctor about the best way to feed 
your baby if you take this medicine. You should not use Segluromet if you are breast-feeding.

Driving and using machines
This medicine has no or negligible influence on the ability to drive and use machines. Taking this 
medicine in combination with insulin or medicines that increase insulin release from the pancreas can 
cause blood sugar levels to drop too low (hypoglycaemia), which may cause symptoms such as 
shaking, sweating and change in vision, and may affect your ability to drive and use machines. Do not 
drive or use any tools or machines if you feel dizzy while taking Segluromet.

Segluromet contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’.

3. How to take Segluromet

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 

How much to take
 The recommended dose of Segluromet is one tablet twice a day. 
 The dose of Segluromet that you take will depend on your condition and the amount of 

ertugliflozin and metformin needed to control your blood sugar. 
 Your doctor will prescribe the right dose for you. Do not change your dose unless your doctor 

has told you to.

Taking this medicine
 Swallow the tablet; if you have difficulties in swallowing the tablet can be broken or crushed.
 Take one tablet twice daily. Try to take it at the same time each day; this will help you 

remember to take it.
 It is best to take your tablet with a meal. This will lower your chance of having an upset 

stomach.
 You need to keep following your food and exercise plan while taking Segluromet.

 



55

If you take more Segluromet than you should
If you take too much Segluromet, talk to a doctor or pharmacist straight away.

If you forget to take Segluromet
If you forget a dose, take it as soon as you remember. However, if it is nearly time for your next dose, 
skip the missed dose and go back to your regular schedule. 

Do not take a double dose (two doses at the same time) to make up for a forgotten dose.

If you stop taking Segluromet
Do not stop taking this medicine without talking to your doctor. Your blood sugar levels may increase
if you stop the medicine.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Contact a doctor or the nearest hospital straight away if you have any of the following serious 
side effects:

Lactic acidosis (very rare, may affect up to 1 in 10,000 people)
Segluromet may cause a very rare, but very serious side effect called lactic acidosis (see section 
“Warnings and precautions”). If this happens, you must stop taking Segluromet and contact a doctor or 
the nearest hospital immediately, as lactic acidosis may lead to coma.

Diabetic ketoacidosis (rare, may affect up to 1 in 1,000 people)
These are the signs of diabetic ketoacidosis (see also section “Warnings and precautions”): 
 increased levels of “ketone bodies” in your urine or blood 
 rapid weight loss 
 feeling sick or being sick 
 stomach pain 
 excessive thirst 
 fast and deep breathing 
 confusion 
 unusual sleepiness or tiredness 
 a sweet smell to your breath, a sweet or metallic taste in your mouth or a different odour to your 

urine or sweat 
This may occur regardless of blood glucose level. Your doctor may decide to temporarily or 
permanently stop your treatment with Segluromet.

Necrotising fasciitis of the perineum or Fournier’s gangrene (not known, cannot be estimated 
from the available data)
A serious soft tissue infection of the genitals or the area between the genitals and the anus (see section 
“Warnings and precautions” for symptoms).

If you notice any of the side effects above, contact a doctor or the nearest hospital straight away.

Contact your doctor as soon as possible if you notice the following side effects:

Dehydration (losing too much water from your body; common, may affect up to 1 in 10 people) 
Symptoms of dehydration include:
 dry mouth
 feeling dizzy, light-headed, or weak, especially when you stand up

 



56

 fainting

You may be more likely to get dehydrated if you:
 have kidney problems
 take medicines that increase your urine production (diuretics) or lower blood pressure
 are 65 years or older

Low blood sugar (hypoglycaemia; common)
Your doctor will tell you how to treat low blood sugar and what to do if you have any of the symptoms 
or signs below. The doctor may lower the dose of your insulin or other diabetes medicine.
Signs and symptoms of low blood sugar may include:
 headache
 drowsiness
 irritability
 hunger
 dizziness
 confusion
 sweating
 feeling jittery
 weakness
 fast heart beat
If you notice any of the side effects above, contact your doctor as soon as possible.

Other side effects include:

Very common
 vaginal yeast infection (thrush)
 feeling sick (nausea)
 vomiting
 diarrhoea
 stomach ache
 loss of appetite

Common 
 yeast infections of the penis
 changes in urination, including urgent need to urinate more often, in larger amounts, or at night
 thirst
 vaginal itching
 change in taste
 blood tests may show changes in the amount of urea in your blood
 blood tests may show changes in the amount of total and bad cholesterol (called LDL - a type of 

fat in your blood)
 blood tests may show changes in the amount of red blood cells in your blood (called 

haemoglobin)

Uncommon (may affect up to 1 in 100 people)
 blood tests may show changes related to kidney function (such as ‘creatinine’)
 painful urination

Very rare 
 decreased vitamin B12 levels. This may cause anaemia (low levels of red blood cells).
 liver function test disorders
 hepatitis (a liver problem)
 hives
 redness of the skin

 



57

 itching

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Segluromet

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister and the carton after EXP.
The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not use this medicine if the packaging is damaged or shows signs of tampering.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Segluromet contains 

 The active substances are ertugliflozin and metformin.
o Each Segluromet 2.5 mg/850 mg film-coated tablet contains 2.5 mg ertugliflozin (as 

ertugliflozin L-pyroglutamic acid) and 850 mg of metformin hydrochloride.
o Each Segluromet 2.5 mg/1,000 mg film-coated tablet contains 2.5 mg ertugliflozin (as 

ertugliflozin L-pyroglutamic acid) and 1,000 mg of metformin hydrochloride.
o Each Segluromet 7.5 mg/850 mg film-coated tablet contains 7.5 mg ertugliflozin (as 

ertugliflozin L-pyroglutamic acid) and 850 mg of metformin hydrochloride.
o Each Segluromet 7.5 mg/1,000 mg film-coated tablet contains 7.5 mg ertugliflozin (as 

ertugliflozin L-pyroglutamic acid) and 1,000 mg of metformin hydrochloride.
 The other ingredients are:

o Tablet core: povidone (K29-32) (E1201), microcrystalline cellulose (E460), crospovidone 
(E1202), sodium lauryl sulfate (E487), magnesium stearate (E470b).

 Film coating:
o Segluromet 2.5 mg/850 mg tablets and Segluromet 7.5 mg/850 mg tablets: hypromellose 

(E464), hydroxypropyl cellulose (E463), titanium dioxide (E171), iron oxide red (E172), 
iron oxide yellow (E172), iron oxide black (E172), carnauba wax (E903).

o Segluromet 2.5 mg/1,000 mg tablets and Segluromet 7.5 mg/1,000 mg tablets: 
hypromellose (E464), hydroxypropyl cellulose (E463), titanium dioxide (E171), iron 
oxide red (E172), carnauba wax (E903).

What Segluromet looks like and contents of the pack
 Segluromet 2.5 mg/850 mg film-coated tablets (tablets) are beige, 18 x 10 mm oval, film-coated 

tablets debossed with “2.5/850” on one side and plain on the other side.
 Segluromet 2.5 mg/1,000 mg film-coated tablets (tablets) are pink, 19.1 x 10.6 mm oval, 

film-coated tablets debossed with “2.5/1000” on one side and plain on the other side.
 Segluromet 7.5 mg/850 mg film-coated tablets (tablets) are dark brown, 18 x 10 mm oval, 

film-coated tablets debossed with “7.5/850” on one side and plain on the other side.
 Segluromet 7.5 mg/1,000 mg film-coated tablets (tablets) are red, 19.1 x 10.6 mm oval, 

film-coated tablets debossed with “7.5/1000” on one side and plain on the other side.

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


58

Segluromet is available in Alu/PVC/PA/Alu blisters. The pack sizes are 14, 28, 56, 60, 168, and 
180 film-coated tablets in non-perforated blisters, multipack containing 196 (4 packs of 49) film 
coated tablets in non-perforated blisters and 30x1 film-coated tablets in perforated unit dose blisters.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel: + 370 5 2780247
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Teл.: + 359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel.: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: + 36 1 888-5300
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: +45 4482 4000
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
MSD SHARP & DOHME GMBH
Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)
e-mail@msd.de

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel: + 372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: + 47 32 20 73 00
msdnorge@msd.no

Ελλάδα
MSD Α.Φ.Β.Ε.Ε.
Τηλ: + 30 210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp. z o.o. 
Tel.: +48 22 549 51 00
msdpolska@merck.com

 



59

France
MSD France
Tél: + 33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: + 351 21 4465700
inform_pt@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o. 
Tel: + 385 1 6611 333
croatia_info@merck.com  

România
Merck Sharp & Dohme Romania S.R.L.

Tel: +40 21 529 29 00

msdromania@merck.com

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 2998700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: + 386 1 5204201
msd_slovenia@merck.com

Ísland
Vistor hf.
Sími: + 354 535 7000

Slovenská republika
Merck Sharp & Dohme, s.r.o.
Tel: + 421 (2) 58282010
dpoc_czechslovak@merck.com

Italia
MSD Italia S.r.l. 
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: + 358 (0)9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 800 00 673
+357 22866700
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tfn: + 46 (0)77 570 04 88
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: + 371 67 364224
msd_lv@merck.com

United Kingdom
Merck Sharp & Dohme Limited 
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

This leaflet was last revised in {MM/YYYY}

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET