Clinical trial NCT02097342: Effect of Linagliptin on Insulin Sensitivity and Pancreatic Beta Cell Function in Patients With Type 2 Diabetes Mellitus
Official title: A Randomized Double-blind Study to Evaluate the Effect of Linagliptin on Pancreatic Beta Cell Function and Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus on Metformin Monotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Insulin Sensitivity/Resistance
Keywords: Type 2 Diabetes Mellitus
Insulin sensitivity- hyperinsulinemic euglycemic clamp
Pancreatic beta cell function
Linagliptin
Voglibose
Mixed meal test
GLP-1 response
Lead sponsor: PIMERIndia
Sponsor class: UNKNOWN
First posted: 2014-03-27
Enrollment: 30
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is planned to evaluate if linagliptin can improve insulin sensitivity in patients with type 2 diabetes mellitus. In addition, the effect of linagliptin on pancreatic function will be studied.

Detailed description: This is a prospective study of 30 patients with type 2 diabetes mellitus (T2DM) . Patients with T2DM in the age group 30-65 years and duration of diabetes less than five years will be screened. After exclusion, those who meet the inclusion criteria will be included in the study.

Once eligibility criteria are confirmed, patients will be educated about their disease and will be advised weight maintenance diabetic diet and exercise throughout the study period. Patients will be randomized to three groups - linagliptin (5mg OD) or voglibose (0.2mg TDS) or placebo OD. Metformin will be continued in all patients. To evaluate the effect of linagliptin on insulin sensitivity and beta cell function, independent of changes in HbA1c, the voglibose group is included. Each group will have 10 patients and will be followed up for 6 months. Both patients and physicians will be blinded to the treatment.

After having written informed consent, a detailed history and a thorough clinical examination will be done in all subjects including measurement of height, weight, body mass index and waist circumference. Hemoglobin, liver function tests, renal function tests, lipid profile, HbA1c, fasting plasma insulin , C-peptide, homeostasis model assessment-insulin resistance index(HOMA-1R) and homeostasis model assessment-beta cell function index (HOMA-β) will be done at baseline. A euglycemic hyperinsulinemic clamp study and a mixed meal test will be performed in all patients (on different days) at baseline and after 6 months of follow up. Biochemical parameters will be measured again 6 months after therapy. Fasting and post-prandial blood glucose will be done monthly for 6 months.

Eligibility criteria: Inclusion Criteria:

* Patients with type 2 diabetes mellitus (according to ADA guidelines)
* Age between 30-65 years
* Duration of diabetes less than five years
* BMI of between 20 and 40 kg/m2
* HbA1c level of \< 7.5%
* On metformin monotherapy for at least 6 weeks

Exclusion Criteria:

* History of ketoacidosis
* Hepatic impairment (defined as plasma aminotransferase elevations of more than 3 times upper limit of normal)
* Renal failure (defined as Serum Creatinine more than 1.5 mg/dl)
* Coronary artery disease or heart failure
* Cerebrovascular disease or stroke
* Anemia (Hb\< 10 g/dl)
* Those who requires insulin therapy HbA1c \>7.5%
* Presence of macular edema
* Pregnant or lactating women
* Patients who have received dipeptidyl peptidase 4 (DPP-4) inhibitor therapy within last 3 months

Primary outcomes:
measure: To study the effect of Linagliptin on insulin sensitivity by performing euglycemic hyperinsulinemic clamp in patients with type 2 diabetes mellitus.
timeFrame: 6 months
Secondary outcomes:
measure: To study the effects of Linagliptin on glycemic control and beta cell function in patients with type 2 diabetes mellitus 6 months
timeFrame: 6 months
Other outcomes:
measure: To study the effect of voglibose on glucagon like peptide1 (GLP1) secretion and insulin resistance in patients with type 2 diabetes mellitus 6 months
timeFrame: 6 months
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education & Research
Study officials:
References:
citation: Parthan G, Bhansali S, Kurpad AV, Walia R, Bhat K, Bhansali A. Effect of Linagliptin and Voglibose on metabolic profile in patients with Type 2 Diabetes: a randomized, double-blind, placebo-controlled trial. BMC Pharmacol Toxicol. 2018 Jul 3;19(1):38. doi: 10.1186/s40360-018-0228-z.