Review: Metformin is linked to reduced mortality in type 2 diabetes with comorbid CKD and CHF

A recent review looked at studies comparing metformin, alone or with other glucose-lowering treatment, with no metformin in adults with type 2 diabetes. All studies included patients with chronic kidney disease (CKD), congestive heart failure (CHF), chronic liver disease (CLD), or older age. The review found that metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment was associated with improvements in key clinical outcomes, supporting recent changes in metformin labeling to treat more patients with these conditions.

The review was published in the Feb. 7 Annals of Internal Medicine. The following commentary by Sina Jasim, MD, MPH, and Steven A Smith, MD, FACP, was published in the ACP Journal Club section of the April 18 Annals of Internal Medicine.

Phenformin, a biguanide prescribed for glycemic control, was withdrawn from the market in the 1970s because of its association with often fatal lactic acidosis, especially among patients with renal disease. Metformin, also a biguanide, has been suspect ever since, without evidence that it shares the same adverse effects and despite strong recommendations for its use as first-line treatment for type 2 diabetes.

The rigorous systematic review and meta-analysis by Crowley and colleagues is consistent with the literature supporting metformin use in patients with diabetes and eGFR as low as 30 mL/min/1.73 m². Meta-analyses showed reduced all-cause mortality in patients with CHF and CKD; no meta-analyses were done for patients with CLD. However, the results are based on available observational studies with moderate to high risk for bias, and the strength of evidence is insufficient to draw solid conclusions.

Metformin is an effective, safe, and inexpensive option for patients with type 2 diabetes. It may reduce risk for cardiovascular events and mortality. As monotherapy, metformin reduces HbA1c levels by 1.12% and seems to have pleiotropic anti-inflammatory effects and improves lipid metabolism related to diabetes complications. The dose was unknown in many of the included studies, and the question of dose adjustment remains valid in patients with specific comorbid conditions. The studies did not include patients with severe CKD (stage 4 to 5), and with the progressive nature of CKD, would metformin continue to be the best choice over the long term? Interindividual patient variation in response to metformin is possible and can be explained by many factors.

The April 18 ACP Journal Club also includes a commentary on ACP's 2017 clinical practice guideline update on metformin.