Metformin: an old but still the best treatment for type 2 diabetes

Abstract

The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin’s mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin’s negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection.

Transporters Involved in Metformin Pharmacokinetics and Treatment Response

“…Metformin and its structurally related analog, phenfomin, are derivatives of guanidine, which was discovered in the extracts of the plant Galega officinalis (French Lilac) in the 1920s 1 . Metformin improves peripheral and liver sensitivity to insulin, reduces glucose production in the liver, increases insulin-stimulated uptake and utilization of glucose by peripheral tissues, decreases appetite, and causes weight reduction 2 . In recent years, new indications for metformin use in clinical practice have emerged.…”

“…In recent years, new indications for metformin use in clinical practice have emerged. In particular, a number of studies have shown that metformin can positively influence multiple cardiovascular disease risk markers, including improvement of serum lipid profiles and modulation of inflammatory markers, and possibly reduce risk for cancer [2][3][4][5] .…”

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities

“…The latter is likely due to a low amount of endogenous DNA damage in the WT mice fed a regular chow diet. Similarly, administration of metformin (Met), the drug used to treat diabetes (31), also suppressed the activation of the DNA damage response, the increase in inflammatory factors, and the metabolic abnormalities in the pol η −/− mice, perhaps because it enhances antioxidant defenses and reduces inflammation (32) (Fig. 2 D and E and Fig.…”

Use of Metformin for Cardiometabolic Risks in Psychiatric Practice: Need-to-Know Safety Issues

“…9 The risk of these adverse effects can be reduced by gradual dose uptitration, by dosing the medication at mealtimes, and by preferring slow-release formulations over immediate-release formulations.…”