Initial combination therapy with metformin and colesevelam for achievement of glycemic and lipid goals in early type 2 diabetes.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of initial combination therapy with metformin plus colesevelam in patients with early type 2 diabetes.

METHODS:

In this 16-week, randomized, double-blind, placebo-controlled study, adults with type 2 diabetes (hemoglobin A1c [A1C] values of 6.5% to 10.0%) and hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] levels > or =100 mg/dL) were randomly assigned (1:1) to colesevelam (3.75 g/d) or placebo in combination with open-label metformin (850 mg/d; uptitrated at week 2 to 1,700 mg/d). The primary efficacy evaluation was change in A1C from baseline to study end (week 16 with last observation carried forward).

RESULTS:

In total, 286 patients were randomized: metformin/colesevelam (n = 145) or metformin/placebo (n = 141). Mean A1C was reduced by 1.1% with metformin/colesevelam (from 7.8% at baseline to 6.6% at study end) and by 0.8% with metformin/placebo (from 7.5% to 6.7%), resulting in a treatment difference of -0.3% at study end (P = .0035). In addition, metformin/colesevelam significantly reduced LDL-C (-16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), apolipoprotein B (-8.0%), and high-sensitivity C-reactive protein (-17%) and increased apolipoprotein A-I (+4.4%) and triglycerides (+18.6%) versus metformin/placebo (P<.01 for all). The proportions of patients who achieved recommended goals with metformin/colesevelam versus metformin/placebo, respectively, were as follows: A1C <7.0% (67% versus 56% [P = .0092]), LDL-C <100 mg/dL (48% versus 18% [P<.0001]), and composite A1C <7.0% + LDL-C <100 mg/dL (40% versus 12% [P<.0001]). Safety and tolerability were similar between the treatment groups.

CONCLUSION:

Metformin plus colesevelam may be a valid option for initial therapy to achieve glycemic and lipid goals safely in early type 2 diabetes.

• Authors: Julio Rosenstock, Vivian A Fonseca, W Timothy Garvey, Ronald B Goldberg, Yehuda Handelsman, Stacey L Abby, Yu-Ling Lai, Xiaoping Jin, Soamnauth Misir, Sukumar Nagendran, Michael R Jones
• Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists (Endocr Pract) 2010 Jul-Aug Vol. 16 Issue 4 Pg. 629-40 ISSN: 1934-2403 [Electronic] United States
• PMID: 20634175 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticholesteremic Agents
• Blood Glucose
• Cholesterol, LDL
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Lipids
• hemoglobin A1c protein, human
• Allylamine
• Metformin
• Colesevelam Hydrochloride

Topics

• Adolescent
• Adult
• Aged
• Allylamine (adverse effects, analogs & derivatives, therapeutic use)
• Anticholesteremic Agents (adverse effects, therapeutic use)
• Blood Glucose (analysis)
• Cholesterol, LDL (blood)
• Colesevelam Hydrochloride
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Double-Blind Method
• Drug Therapy, Combination (adverse effects)
• Female
• Glycated Hemoglobin (analysis)
• Humans
• Hypoglycemic Agents (adverse effects, therapeutic use)
• Lipids (blood)
• Male
• Metformin (administration & dosage, adverse effects, therapeutic use)
• Middle Aged
• Time Factors
• Young Adult