bluuebunny/crossref_metadata_2025_split huggingface dataset:
1096-P: Determining the Optimal Fasting Glucose Target for Patients with Type 2 Diabetes: Results of the FPG Goal Trial
Authors: YANG WENYING , MA JIANHUA , YUAN GUOYUE , LI LING , ZHANG MIN , LU YIBING , YE XINHUA , SONG WEIHONG , LIU MING , WU JUN , CHEN RIQIU , CUI NAN , LI YUNGUANG , ZHANG XIA , YANG JIN-KUI 
Published: June 2019

Background: The optimal fasting glucose target to achieve an HbA1c &lt;7.0% in patients with T2D remains controversial.
Methods: This open-label RCT conducted in China (ClinicalTrials.gov, NCT02545842), randomly assigned (1:3:3) adults (aged 18-65 years) with uncontrolled T2D (HbA1c &gt;7% to ≤10.5%) on 1-3 OADs to 1 of 3 self-monitored fasting blood glucose (FBG) target groups: ≤5.6 mmol/L (Group 1), ≤6.1 mmol/L (Group 2), or ≤7.0 mmol/L (Group 3). The lowest of 3 consecutive FBG values was used for insulin glargine 100 U/ml titration decisions. Primary endpoint was the proportion of patients achieving an HbA1c &lt;7.0% at 24 weeks.
Results: Of 947 patients randomized (Group 1, n=136; Group 2, n=405; Group 3, n=406), 914 were analyzed (mean age 53.9 years; 56.2% male; mean HbA1c 8.59%), and 885 (93.4%) completed the study. At 24 weeks, 44.4%, 46.1%, and 37.7% of patients achieved an HbA1c &lt;7.0% in Group 1, 2, and 3, respectively (p=0.017; Group 2 vs. Group 3). Significantly more patients in Group 2 than in Group 3 (45.0% vs. 36.5%; p=0.014) achieved an HbA1c &lt;7% without hypoglycemia (BG ≤3.0 mmol/L). Confirmed hypoglycemia (BG ≤3.9 mmol/L) was significantly more frequent in Group 1 vs. Group 3 (38.9 vs. 23.3%, p&lt;0.001) but not in Group 2 vs. Group 3 (27.5% vs. 23.3%; p=0.177). Based on the lowest of 3 consecutive FBG values, the proportions of patients achieving an FBG within their target range at 24 weeks were 70.1%, 67.6% and 79.0% in Groups 1, 2 and 3, respectively. However, based on laboratory fasting plasma glucose (FPG) measurements, these proportions were 31.9%, 39.5% and 47.7%. After re-dividing by actual FPG level at 24 weeks, significantly more patients with an FPG ≤5.6 mmol/L (68.7%, p&lt;0.001) and 5.6&lt; FPG ≤6.1mmol/L (58.2%, p=0.013) achieved an HbA1c &lt;7.0% than those with 6.1&lt; FPG ≤7.0 mmol/L (43.6%).
Conclusions: The optimal FBG target for the majority of patients with T2D appears to be ≤6.1 mmol/L. However, for patients at lower risk of hypoglycemia, an FBG target of ≤5.6 mmol/L may be appropriate.

Disclosure
W. Yang: Speaker's Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi, Servier. J. Ma: None. G. Yuan: None. L. Li: None. M. Zhang: None. Y. Lu: None. X. Ye: Speaker's Bureau; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk Inc. W. Song: None. M. Liu: None. J. Wu: None. R. Chen: None. N. Cui: Employee; Self; Sanofi. Y. Li: Employee; Self; Sanofi. X. Zhang: None. J. Yang: None.
1101-P: The Effect of Smoke on Short-Term Insulin Intensive Therapy for Male Patients with New Diagnosis Type 2 Diabetes
Authors: WAN XUESI , HUANG ZHIMIN , LIU LIEHUA , LI YANBING 
Published: June 2019

Our previous study showed that short-term intensive insulin therapies (SIIT) can improve insulin resistance by eliminating glucolipotoxicity and induce remission in newly diagnosed T2DM patients. It's interesting that smokers seem to recover worse than non-smokers. The purpose of this study is to clarify the effect of smoking on T2DM remission from SIIT. 103 male patients (aged 47±10 ys, HbA1C 11.2±2.1%, 59 smokers) after 2-week SIIT therapy were studied. At the 1-year follow-up, the remission rate was much lower in the smokers than non-smokers (36/59 vs. 35/44). Though their insulin secretion and HbA1C were similar at the end of therapy, the smokers have statistically higher TG and worse HOMA-IR. These results indicated that smoking might affect the remission rate mainly by the weaker improved metabolism of lipids.

Disclosure
X. Wan: None. Z. Huang: None. L. Liu: None. Y. Li: None.
1110-P: Use of IDegLira Is Associated with High Persistency Rates Up to 12 Months (M) and Improved A1C after 6M in Swedish Clinical Practice
Authors: ELIASSON BJORN , EKELUND JAN , SVENSSON ANN-MARIE , MIFTARAJ MERVETE , MÅRDBY ANN-CHARLOTTE , ROCHA FERNANDES JOAO DIOGO DA 
Published: June 2019

This retrospective study examines outcomes associated with use of IDegLira - a fixed-ratio insulin degludec/liraglutide combination - in a large real-world cohort of patients with type 2 diabetes in Sweden. Data were obtained from the Swedish National Diabetes Registry on patients who initiated IDegLira (index date) until the end of 2017 (or 30 June/1 January 2017 for 6M/12M for persistency analyses). Persistency at 6M was defined as ≥1 more IDegLira withdrawal within 6M of index date, and 12M persistency was ≥1 more withdrawal in M6-12. Clinical variables were assessed at baseline (closest measurement to index date in previous 12M) and 6M ± 45 days after IDegLira initiation. Mean daily IDegLira dose was calculated from volume withdrawn during defined time periods of ≥6M. Baseline characteristics for overall cohort (N=3000) are in Table. At 6 and 12M, 2281/2432 (94%) and 1482/1760 (84%) patients were persistent, respectively. In persistent patients, least squares mean [95% CI] change in A1C and body mass index was -0.9% [-1.0; -0.8] and -0.3 kg/m2 [-0.5; -0.2] at 6M, respectively and mean daily IDegLira dose was 32-35 U at all 180-day periods assessed (Table). After 6M, IDegLira use in Sweden is associated with improved A1C and no clinically significant change in BMI at a moderate mean daily insulin dose, and 84% were persistent at 12M.

Disclosure
B. Eliasson: Advisory Panel; Self; Amgen Inc., AstraZeneca, Merck Sharp & Dohme Corp. Speaker's Bureau; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. J. Ekelund: Employee; Spouse/Partner; AstraZeneca. Stock/Shareholder; Spouse/Partner; AstraZeneca. A. Svensson: None. M. Miftaraj: None. A. Mårdby: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J. da Rocha Fernandes: Employee; Self; Novo Nordisk A/S.

Funding
Novo Nordisk A/S
1123-P: Reduction of Mortality and Major Adverse Cardiovascular Events (MACE) in Men with Hypogonadism and Type 2 Diabetes (T2DM) Receiving Long-Term Treatment with Injectable Testosterone Undecanoate (TU): Ten-Year Data from a Urological Registry Study
Authors: HAIDER KARIM S. , HAIDER AHMAD , SAAD FARID 
Published: June 2019

Background: Potential cardiovascular risk as a result of testosterone therapy is controversially discussed.
Methods: In a registry of 823 men with hypogonadism, 324 men (39%) had T2DM. 152 received TU 1000 mg/12 weeks (T-group), 172 opted against treatment (CTRL). Changes over time between groups were compared by mixed effects model for repeated measures with random effect for intercept and fixed effects for time, group and their interaction, and adjusted for age, weight, WC, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the two groups.
Results: Mean age: T-group: 61.8±5.1, CTRL: 63.6±4.9 years.
Follow-up: T-group (CTRL): mean: 7.4 (8.3), median: 8 (9) years. T-group: 54 patients (35.5%) had had a previous cardiovascular disease (CVD, defined as myocardial infarction, stroke, or diagnosis of coronary artery disease). CTRL: 68 patients (39.5%) (p=0.4574). 64 men (42.1%) had been smokers at baseline (T-group), 66 (38.4%) in CTRL (p=0.4939). Most classical risk factors were significantly higher at baseline in the T-group compared to CTRL: BMI (36.4±4.5 vs. 33.3±5.3 kg/m²), systolic blood pressure (162.6±13.1 vs. 145.4±14.7 mmHg), diastolic blood pressure (97.2±10.7 vs. 84.7 vs. 10.3 mmHg), LDL (4.6±0.7 vs. 4.0±1.4 mmol/L), with no significant difference in HDL. Glycemic control was worse in the T-group: HbA1c 9.1±1.2 vs. 7.8±0.7%, HOMA-IR 10.2±2.1 vs. 7.5±1.3. Mortality: during the entire observation time, 12 patients (7.8%) died in the T-group and 43 (25%) in CTRL (p&lt;0.0001). MACE: in the T-group, there were no myocardial infarctions or strokes. In CTRL, 49 myocardial infarctions (28.5%) and 42 strokes (24.4%) occurred.
Conclusions: Mortality, myocardial infarctions and strokes were reduced in men with hypogonadism and T2DM receiving long-term testosterone therapy.

Disclosure
K.S. Haider: Speaker's Bureau; Self; Bayer AG. A. Haider: Research Support; Self; Bayer AG. Speaker's Bureau; Self; Bayer AG. F. Saad: Employee; Self; Bayer AG. Stock/Shareholder; Self; AbbVie Inc., Amgen Inc., Bayer AG.

Funding
Bayer AG
1125-P: Effect of High Dose vs. Conventional Dose Angiotensin Receptor Blockers in 175 T2DM with Microalbuminuria on CV (NT-ProBNP) and Renal Biomarkers
Authors: GUPTA VISHAL , TELI VAISHALI 
Published: June 2019

Methodology: 175 T2DM patients on regular follow-up with microalbuminuria (eUACR &gt;30), aged &lt;75 years, irrespective of their A1c, on standard glucose, lipid and blood pressure lowering therapy using ARB (valsartan or telmisartan) were followed-up for 2 years. 2 groups were identified, Control group (Cn) on conventional dose CDARB’s and case (Cs) group on high dose HDARB’s. Renal (creatinine, eGFR, UACR) and CV (SBP, DBP, BMI, Lipid profile, hs-CRP) parameters were evaluated in both groups at 3-6 monthly intervals. NT-ProBNP was evaluated in both groups at the end of the study. Patients with history of any revascularization, IHD or hospitalization in last 1 year, eGFR &lt;45, hyperkalemia &gt;5.5 were excluded. Data was analysed using PSPP version 1.0.1 and represented as Mean (Standard deviation), independent sample t-test and paired t test was used. P-value of 0.05 was considered significant.
Results: Both groups Cs and Cn were well matched for treatment and clinical characteristics except DBP, higher mean in Cs (81 ±11.39) vs. Cn (76.80 ± 11.58, p 0.025). Mean CDARB dose in Cn group (Telmisartan 55.15mg (SD ± 24) and valsartan 115.76 (SD ±47.82) vs. Cs group HDARB (telmisartan 222.22mg (SD±49.22) and valsartan 334.58 (SD±77.81). Within the cases there was a significant reduction seen in A1c, SBP, hs-CRP, lipid parameters and UACR over 2 years. Within the control group there was a significant reduction seen in A1c, lipid parameters, UACR. At the end of the follow-up there was significant reduction seen in Cs in LDL (Cs 51.34 ±19.73 vs. Cn 63.82 ± 25.97, p-0.005) and non-HDL (Cs 66.77 ±34.74 vs. Cn 51.70 ±44.56, p-0.023). There was a trend towards reduction in hs-CRP in Cs (Cs 1.74 ± 1.92 vs. Cn 2.53 ± 3.70, p-0.066). The NT-ProBNP remained high in both groups (142.86 ±232.32 vs. 192.61 ±260.93, p-0.203).
Conclusion: HDARB may be associated with better vascular protection as shown by improvements in LDL, non-HDL and hs-CRP compared to CDARB in T2DM with microalbuminuria.

Disclosure
V. Gupta: None. V. Teli: None.
1128-P: SGLT2 Inhibition Increases Serum Copeptin in Adults with Type 1 Diabetes (T1D)
Authors: LYTVYN YULIYA , BJORNSTAD PETTER , KATZ ALEXANDRA , SINGH SUNITA K. , GODOY LUCAS C. , CHUNG LINH T. , VINOVSKIS CARISSA L. , PERKINS BRUCE A. , CHERNEY DAVID 
Published: June 2019

Elevated copeptin, a stable surrogate of vasopressin, is recognized to be higher in T1D and predicts diabetic kidney disease and cardiovascular (CV) mortality. Vasopressin increases renal oxygen consumption through enhanced sodium reabsorption and may result in renal hypoxia. Given the natriuretic and cardiorenal protective effects of SGLT2 inhibition (SGLT2i) in clinical trials, our aim was to: 1) examine serum copeptin in adults with T1D after SGLT2i with empagliflozin (EMPA) for 8-weeks; and 2) determine the relationship between copeptin and metabolic, renal and system hemodynamic parameters.
In this post hoc, exploratory analysis, serum copeptin concentration, glomerular filtration rate (GFR) by inulin clearance, effective renal plasma flow (ERPF) by PAH clearance, vascular stiffness parameters, plasma RAAS markers, HbA1c, 24-hour urine volume and sodium and glucose excretion were measured in 40 participants with T1D (24.1±5.0 years, HbA1c 8.0±0.9%) during eu- and hyperglycemia at baseline and after 25 mg of daily EMPA.
Copeptin concentrations increased under both eu- and hyperglycemic conditions (4.0±2.1 to 5.1±6.0 pmol/L, p=0.005 and p&lt;0.0001, respectively) in response to EMPA. Higher copeptin concentrations were associated with higher HbA1c (β±SE: 0.97±0.30, p=0.003), lower 24h urine volume (β±SE: -3.08±1.05, p=0.006) and fractional sodium excretion (β±SE: -8.30±2.73, p=0.004), after correcting for age, sex, systolic blood pressure (SBP), and HbA1c. There were no significant relationships between copeptin and RAAS markers, vascular stiffness, renal or systemic hemodynamic parameters in fully adjusted models.
SGLT2i increased serum copeptin concentrations, which positively correlated with HbA1c and inversely with urine output and natriuresis, but not with renal or system hemodynamic parameters. Further work is required to evaluate the clinical implications of elevated copeptin with SGLT2i; whether it is simply a marker of diuresis or may contribute to CV disease long-term.

Disclosure
Y. Lytvyn: None. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. A. Katz: None. S.K. Singh: None. L.C. Godoy: None. L.T. Chung: None. C.L. Vinovskis: None. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi.
113-LB: Effects of Liraglutide and Empagliflozin Add-On to Insulin Therapy in Patients with Type 2 Diabetes: ELLENA-IT, a Randomized Controlled Study
Authors: NAKAGUCHI HIROTATSU , KONDO YOSHINOBU , TERAUCHI YASUO 
Published: June 2019

Liraglutide (Lira) and empagliflozin (Empa) have been reported to suppress cardiovascular events in large-scale clinical trials. However, reports of their long-term combined use with insulin therapy or direct comparisons of both drugs are limited. This open-label, parallel-group, randomized controlled trial aimed to compare the effects of Lira and Empa used in combination with insulin therapy in patients with type 2 diabetes (T2D). Adult outpatients with T2D undergoing stable insulin therapy with HbA1c level of 7.0%-9.5% were eligible for participation. Subjects received 0.9 mg/day Lira or 10 mg/day Empa for 24 weeks. The primary endpoint was the change in HbA1c levels from baseline to week 24. Body composition was assessed using the dual energy X-ray absorptiometry method (UMIN-CTR 000027614). Overall, 66 insulin-treated patients with T2D were randomized to receive Lira or Empa; 57 patients completed 24 weeks of weekly administration of Lira (n = 29) or Empa (n = 28). HbA1c and glycated albumin (GA) levels were lower in the Lira group than in the Empa group (HbA1c, Lira, −1.23 ± 0.85% vs. Empa, −0.32 ± 0.68%, p &lt; 0.001; GA, Lira, −4.3 ± 3.1% vs. Empa, −2.2 ± 2.9%, p = 0.01). There was no difference between the two groups in terms of change in body weight (∆BW: Lira, −1.4 ± 1.9 kg vs. Empa, −1.4 ± 1.9 kg, p = 0.97) or in body fat mass/lean tissue mass. There was no difference between the groups in terms of change in urinary albumin excretion [∆UAE (median, IQR): Lira, −6.2 (−63.5, −10.1) mg/g-creatinine vs. Empa, −20.4 (−69.7, −2.0) mg/g-creatinine, p = 0.28]. There was no significant difference in the frequency of hypoglycemia between the groups over 24 weeks (p = 0.46).
In conclusion, the addition of Lira to ongoing insulin therapy significantly reduced HbA1c and GA levels to a larger extent than the addition of Empa in patients with inadequately controlled T2D.

Disclosure
H. Nakaguchi: None. Y. Kondo: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.
1136-P: Chemical Pancreatectomy as a Revolutionary Therapy for Chronic Pancreatitis and Prevention of Type 3C Diabetes
Authors: SALEH MOHAMED , KALSI RANJEET S. , GITTES GEORGE 
Published: June 2019

Background: Chronic pancreatitis (CP) is a debilitating disease that leads to chronic pain, pancreatic endocrine and exocrine dysfunction. CP affects &gt; 140,000 in the U.S. and millions worldwide. Type 3C diabetes, a brittle form of diabetes, constitutes 9% of those hospitalized with diabetes. Total pancreatectomy with auto islet cell transplantation (TPIAT) may treat CP and preserve endocrine function, but it is major surgery, the outcomes are variable, and islet yield is questionable.
Methods: An intrapancreatic infusion of 150 µL of acetic acid or sham was performed on 8-week old CD1 mice. Serum enzymes, GTT, GSIS, behavioral pain assessment, histology and IHC were done 4 weeks and 8 weeks after surgery.
Results: There was no significant difference between the two groups in serum amylase and lipase, GTT, GSIS, and pain parameters. IHC revealed negative staining for amylase and normal insulin staining while histology showed intact islets, replacement of acinar cells with fat cells, and no signs of inflammation.
Conclusion: This procedure may be a revolutionary non-invasive therapy for CP able to relieve pain and preserve endocrine function. It may rescue ailing islets by removing the source of injury (exocrine tissue) without major surgery. The loss of the exocrine tissue is trivial because it is not functional, and most patients with CP require enzyme replacement therapy.

Disclosure
M. Saleh: None. R.S. Kalsi: None. G. Gittes: None.
1145-P: Acarbose-Induced Glucagon-Like Peptide-1 Secretion Contributes to the Glucose-Lowering Effect of Acarbose
Authors: DALSGAARD NIELS B. , GASBJERG LÆRKE S. , HANSEN LAURA S. , HANSEN NINA L. , STENSEN SIGNE , HARTMANN BOLETTE , HOLST JENS J. , VILSBØLL TINA , KNOP FILIP K. 
Published: June 2019

The glucose-lowering alpha-glucosidase inhibitor acarbose, is believed to act by delaying digestion and absorption of dietary carbohydrates. It has been shown that acarbose increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes (T2D). In a double-blinded, placebo-controlled, randomized, cross-over study, 15 participants with metformin-treated T2D (age 57-85 years, BMI 23.6-34.6 kg/m2, HbA1c 40-74 mmol/mol (5.8-8.9%)) were subjected to two 14-day treatment periods with acarbose (uptitrated to 100 mg TID) and placebo treatment, respectively, with an interposed 6-week wash-out period. At the end of each treatment period, we performed two randomized 4-hour mixed meal tests (including acetaminophen for evaluation of gastric emptying) with concomitant infusion of exendin(9-39)NH2 (1000 pmol/kg/min for 20 min followed by 450 pmol/kg/min for 240 min) and saline, respectively. Acarbose treatment lowered fasting plasma glucose (P&lt;0.0001) and postprandial plasma glucose excursions (P&lt;0.0001) compared to placebo. Furthermore, acarbose almost doubled the postprandial GLP-1 response (P=0.0032), reduced postprandial glucose-dependent insulinotropic polypeptide (P&lt;0.0001) and delayed gastric emptying (P=0.0395). No absolute difference was seen in exendin(9-39)NH2-induced postprandial plasma glucose changes between treatment periods (P=0.54), but relative to postprandial glucose tolerance during exendin(9-39)NH2 infusions, the change (i.e., contribution of GLP-1) was significantly higher during acarbose (56±26%) compared to placebo treatment (37±15%) (P=0.042). We conclude that acarbose treatment robustly stimulates GLP-1 secretion in patients with T2D and that acarbose-induced GLP-1 secretion contributes to the glucose-lowering effect of acarbose.

Disclosure
N.B. Dalsgaard: None. L.S. Gasbjerg: Stock/Shareholder; Self; Antag Therapeutics. L.S. Hansen: None. N.L. Hansen: None. S. Stensen: None. B. Hartmann: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. T. Vilsbøll: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S.
1149-P: A1C Goal Attainment after Metformin (MET) Uptitration With and Without Sitagliptin (SITA): Impact of Baseline and Target A1C
Authors: CRUTCHLOW MICHAEL , LIN JIANXIN , LAM RAYMOND L. , O'NEILL EDWARD A. , KAUFMAN KEITH D. , ENGEL SAMUEL S. 
Published: June 2019

MET is generally recommended as the initial AHA for T2D, but many patients do not achieve glycemic goal at an initial, sub-maximal dose (500-1000 mg/day) and should intensify therapy. Typically, MET dose is first maximized, followed by addition of a second AHA as needed. This sequential approach can result in prolonged exposure to hyperglycemia. Therefore, addition of a second AHA during MET up-titration may be appropriate for some patients. In a recent study, patients with T2D not at glycemic goal on 1000 mg/day MET initiated SITA or PBO while increasing MET dose to 2000 mg/day. Study participants had entry A1C ≥7.5% (mean = 8.6%) and baseline characteristics were balanced. SITA provided greater improvement in glycemic control and likelihood of A1C goal attainment, with similar safety and tolerability compared to PBO. In a post hoc analysis characterizing the impact of baseline A1C, A1C goal, and treatment on A1C goal attainment, the likelihood of A1C goal attainment decreased as distance to goal at baseline increased (Table). Compared to MET increase alone, MET increase + SITA was generally more effective in achieving glycemic targets across a range of goals and baseline A1C. These results suggest that the distance to A1C goal should be considered throughout the process of MET up-titration to inform AHA intensification strategy, including the potential benefit of early SITA initiation.

Disclosure
M. Crutchlow: Consultant; Spouse/Partner; Crinetics, Novartis Pharmaceuticals Corporation, ProSciento, Soleno Therapeutics, Zealand Pharma A/S. Employee; Self; Merck & Co., Inc. Research Support; Spouse/Partner; Dexcom, Inc. J. Lin: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. R.L. Lam: Employee; Self; Merck & Co., Inc. E.A. O'Neill: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. K.D. Kaufman: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc.

Funding
Merck & Co., Inc.