Metformin: Stepchild of Diabetes Care

The Merriam Webster definition of Stepchild is: “one that fails to receive proper care or attention”. We all know that metformin is pretty much a ‘given’ when we initiate care for diabetes based on nearly all type 2 diabetes treatment guidelines. We also know that metformin has been used effectively in diabetes prevention in patients with prediabetes with long-term effectiveness (1) and that this effect was dose and adherence related (2). Yet despite this, one survey suggested that only 36% of primary care providers prescribe metformin for patients with prediabetes at all (3). Combine this with the fact that we that there is a relationship of dose to the intensity of the hypoglycemic effect in diabetes in clinical trials (4) and that there is an association of glucose control in early treatment with ‘regression’ of pre-diabetes (5).

Guidelines are clear on the need to aggressively intensify therapy in patients with newly diagnosed type 2 diabetes to get to the A1C goal, but patients and physicians may feel less urgency early in the course of the disease, and ‘clinical inertia’ or lack of appreciation of the benefits of early control mean that many patients will be at increased risk of later cardiovascular complications from inadequate intensity of metformin dosing even in the few years subsequent to diagnosis (6). With more recent publications suggesting more flexibility in dosing metformin in patients with impaired renal function, we have even more reason to be comfortable with dosing this important medication (7). When was the last time you recommended metformin for a patient with prediabetes? When was the last time your reviewed your type 2 diabetes patients’ doses of metformin and pushed the envelope on dosing? Sounds like there’s a need to me!

1. Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study Lancet. 2009 November 14; 374(9702): 1677

2. The Diabetes Prevention Program Research Group. Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012;35:731

3. Mainous AG, et al. Prediabetes Screening and Treatment in Diabetes
Prevention: The Impact of Physician Attitudes. J Am Board Fam Med 2016;29:663

4. Hirst JA, et al. Quantifying the Effect of Metformin Treatment and Dose on Glycemic Control. Diabetes Care 2012;35:446

5. Perreault L, et al. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet 2012;379:2243

6. Svensson E, et al. Early Glycemic Control and Magnitude of HbA1c Reduction
Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators. Diabetes Care 2017;40_online April 17

7. Inzucchi, SE, et al. Metformin in Patients With Type 2 Diabetes and Kidney Disease: A Systematic Review. JAMA. 2014;312:2668