Cardiovascular Implications of Antihyperglycemic Therapies for Type 2 Diabetes

Background: Several risk factors for cardiovascular disease (CVD), including insulin resistance/hyperinsulinemia, hyperglycemia, overweight/obesity, dyslipidemia, and hypertension, are often present in varying combinations in patients with type 2 diabetes mellitus (DM). Patients with a clustering of these risk factors, termed the metabolic syndrome, are at greater risk for CVD than are patients with only a single risk factor. Although glycemic control is the central feature of type 2 DM management, patients require an individualized approach to therapy that takes their other CVD risk factors into account. Objective: This review examined the effects of antidiabetes therapy on glycemic control, as well as its potential to affect body weight, serum lipids, and blood pressure (BP), and thus CVD risk. Methods: Information was obtained by searching the MEDLINE and EMBASE databases from 1995 through March 2010. The search terms included type 2 DM, metabolic syndrome, CV complications of type 2 DM, and therapy for type 2 DM. Articles that described relevant details of the metabolic syndrome, CV complications of type 2 DM, and effects of antidiabetes therapy on glycosylated hemoglobin, body weight, serum lipids, and BP were selected for in-depth review. Only English language publications were reviewed. Clinical trials, meta-analyses, and review articles on the key words were preferentially selected for review and analysis. Non English language publications, case reports, letters to the editor, and similar types of publications were excluded. Results: Although all approved antidiabetes agents lowered glucose, their effect on other CV risk factors, such as BP, lipids, and weight, differed significantly. Therapy with insulin, the sulfonylureas, and the thiazolidinediones was associated with weight gain. Metformin and the dipeptidyl-peptidase-4 inhibitors were generally considered weight neutral, whereas the glucagon-like peptide-1 receptor agonists and amylin agonists were associated with weight loss. Metformin, sulfonylureas, thiazolidinedioness, and dipeptidyl-peptidase-4 inhibitors had modest effects on serum lipid levels and BP. The glucagon-like peptide-1 receptor agonists generally had beneficial effects on serum lipid levels and systolic and diastolic BP. Conclusion: A wide variety of agents were available to aid glycemic control in patients with type 2 DM. These agents had variable effects on known CV risk factors that might be present in this patient population, including excess body weight, elevated BP, and increased serum lipids. Some of the newer agents improved glycemic control while also having potentially favorable effects on these CV risk factors. The impact of various agents on known CV risk factors should be considered when selecting a therapeutic regimen. (Clin Then 2011;33:393-407) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.