A comparative study of three different classes of drugs used I the treatment of diabetes mellitus. Classes are: sulphonylureas, thiazolidinediones and DPP-IV inhibitors.
- Conditions
- Type 2 Diabetes Mellitus
- Registration Number
- CTRI/2015/03/005596
- Lead Sponsor
- J N Medical College
- Brief Summary
Diabetes mellitus (DM) refers to a groupof common metabolic disorders that share the phenotype of hyperglycemia.Several distinct types of DM exist and are caused by a complex interaction ofgenetics and environmental factors. Depending on the etiology of the DM,factors contributing to hyperglycemia include reduced insulin secretion,decreased glucose utilization, and increased glucose production.(1)
**Pathophysiology of type 2 diabetesmellitus**
Type 2 DM is characterized by impairedinsulin secretion, insulin resistance, excessive hepatic glucose production,and abnormal fat metabolism. Obesity, particularly visceral or central (asevidenced by the hip-waist ratio), is very common in type 2 DM (2)
The pathophysiology of type 2 diabetesincludes, impaired insulin secretion, impaired insulin action, insulinresistance (3) and impaired incretin effect on β-cell function andnon-suppression of the action of α-cells, with rising blood glucose levels.
Most important biochemical perturbationsin type 2 diabetes mellitus involves peripheral and hepatic insulin resistance,and impaired β-cell function. In type 2 diabetes, adipose tissue in general andvisceral fat in particular, exhibits a decreased inhibition of lipolysis andincreased lipoprotein lipase activity, both resulting in a heightened flux offatty acids in the liver and other tissues.
The skeletal muscle glucose utilizationis impaired to a greater degree than adipose tissue in type 2 diabetes (4).This leads to impaired post-prandial glycogen deposition in muscles. The causeof this resistance is a high free fatty (FFA) concentration in the myocytes.
The hepatic insulin resistance leads toenhanced gluconeogenesis and glucogenolysis leading to increased hepaticglucose production, a hallmark of uncontrolled diabetes.
In type 2 diabetics, rapid meal-relatedinsulin secretion (approx. 30 mins post-meal) is attenuated. Also, there isimpaired rapid oscillation of insulin without any glycemic stimulus. The β-cellmass appears to be slightly reduced at the time of diagnosis. However, thefunctional capacity is impaired out of proportion to its mass.
Other pathogenetic mechanism involvesincretins – a group of hormones secreted by gastrointestinal tract. Twoextremely well known members glucagon like peptide (GLP-1) and glucosedependent insulinotropic peptide (GIP). The former is secreted from L cells ofileum and latter from the K cells located in the proximal small intestine.These hormones account for the enhanced insulin secretory response uponingestion of glucose orally, as compared to that obtained by intravenousglucose administration. This has been termed the incretin effect (5). In thetype 2 diabetes, the incretin effect is blunted, which can be corrected byinjecting GLP-1 or its longer acting analogue, like exenatide or liraglutide.GLP-1 is normally destroyed by a group of enzymes called dipeptyl peptidases,of which dipeptyl peptidase-IV (DPP-IV) is the predominant one. Compoundsinhibiting DPP-IV inhibitors prolong the effect of endogenous GLP-1 and arebeing used therapeutically at present.
Thiazolidinediones regulatetranscription of genes involved in lipid and glucose metabolism, and isexpressed in all insulin sensitive tissues even in pancreatic beta cells butmainly in adipocytes. TZDs stimulates PPAR-gammaagonists, increases number of small, insulin sensitive adipocytes whichenhances glucose uptake, improves glycemic status, improve insulinsensitivities and protect beta cells by lowering the demand on, glucotoxicityand lipotoxicity(6)
Sulphonylureas bind to a specific siteon the βcell KATP channel complex (the sulfonylurea receptor, SUR) andinhibit its activity.
***Anti-diabetic drugs to be used***
1) Agentsstimulating insulin release (secretagogues)
(A) Suphonylureas
Glibenclamide, Glipizide, Gliclazide and Glimepirid
(B) DPP-IV inhibitors
Sitagliptin, Vildagliptin and Saxagliptin
2) Agentslowering insulin resistance (sensitisers)
(A) Biguanides: Metformin
(B) Thiazolidinediones:Pioglitazone and Rosiglitazone
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- All
- Target Recruitment
- 100
- •Newly detected type 2 DM patients.
- •Poorly controlled diabetics on oral hypoglycaemic agents.
•Type 1 Diabetes Mellitus •Diabetic Nephropathy •Diabetic Ketoacidosis (DKA) •Patients on insulin •Congestive Heart Failure (CHF) •Acute infection •Psychotic patient •Pregnancy •HIV / HBsAg / Anti-HCV and immuno-compromised patient.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 3.Plasma Glucose (PG) baseline, 6 weeks, 12 weeks, 18 weeks and 24 weeks Fasting PG baseline, 6 weeks, 12 weeks, 18 weeks and 24 weeks 2 hours PPG baseline, 6 weeks, 12 weeks, 18 weeks and 24 weeks 4.Lipid Profile ( TC, TG, HDL, LDL, VLDL ) baseline, 6 weeks, 12 weeks, 18 weeks and 24 weeks 5.Liver Function Test (LFT) baseline, 6 weeks, 12 weeks, 18 weeks and 24 weeks 1.Haemogram baseline, 6 weeks, 12 weeks, 18 weeks and 24 weeks 2.Glycosylated Hemoglobin HbAâ‚c baseline, 6 weeks, 12 weeks, 18 weeks and 24 weeks
- Secondary Outcome Measures
Name Time Method Electrocardiogram (ECG) C-reactive protein (CRP)
Trial Locations
- Locations (1)
OPD and IPD of department of Medicine and department of Pharmacologyy
🇮🇳Aligarh, UTTAR PRADESH, India
OPD and IPD of department of Medicine and department of Pharmacologyy🇮🇳Aligarh, UTTAR PRADESH, IndiaDr Sanjog Narain TewariPrincipal investigator9760434368sanjogtewari@gmail.com