A variety of medications for type 2 diabetes: comparison of the efficacy and drawbacks

The aim of this review was to summarize the benefits and harms of several drugs commonly used for the treatment of adults with type 2 diabetes mellitus (T2DM).

Treatment for T2DM usually starts with diet changes and exercise because it is largely associated with obesity. Treating T2DM with medications aims to lower blood glucose levels. Medications can stimulate the pancreas to produce more insulin, increase the sensitivity to insulin, or reduce glucose release and absorption into the bloodstream.

Most of the drugs for T2DM are taken orally apart from insulin, which is normally injected. A couple of different oral medications are often prescribed with insulin, in order to increase their effect.

This paper reviews the results of 166 clinical trials and studies that evaluated the efficacy of numerous drug combinations for T2DM. Some of the studied drugs include meglitinides (nateglinide [Starlix], repaglinide [Prandin, NovoNorm, GlucoNorm]) and sulfonylureas (glimepiride [Amaryl]), both designed to increase insulin release from the pancreas. Others are thiazolidinediones (rosiglitazone [Avandia], pioglitazone [Actos]) and metformin (Glucophage), which increase organ sensitivity to insulin. The main effect of metformin is to reduce glucose production by the liver (called 'hepatic gluconeogenesis'). Two newer types of medication include DPP-4 inhibitors (sitagliptin [Januvia], linagliptin [Tradjenta]) and GLP-1 receptor agonists (exenatide [Byetta, Bydureon]), both of which increase insulin production, and sensitize tissues to insulin activity.

Taken together, results from the included studies show that all classes of medication reduced almost equally blood glucose levels. GLP-1 agonists registered weight loss in comparison with the weight gain seen in patients treated with sulfonylureas. Patients treated with sulfonylureas also had a higher risk of hypoglycemia (a life-threatening drop in blood glucose level). Patients treated with thiazolidinediones had a higher risk of heart failure compared to those treated with sulfonylureas and a higher risk of bone fracture compared to those treated with metformin. Metformin reduced cholesterol in addition to glucose levels.

Overall results show that metformin should be the first given medication for the treatment of T2DM. Other medications and combinations reduce glucose levels to the same extent but have more side effects and greater risk of hypoglycemia.

The study has some limitations. One of them is that only English-written publications were reviewed. Moreover, many studies were small, of short duration, and had limited ability to assess clinically important harms and benefits.