- Jennifer Middleton, MD, MPH
The list of medications that help diabetic patients live longer (and not just lower their A1C) got a little longer recently. The March 1 issue of AFP includes a POEM demonstrating reduced mortality with empagliflozin in patients with type 2 diabetes and known cardiovascular disease (CVD).
In this trial, about 7000 patients with both type 2 diabetes and CVD were randomized to receive either one of two doses of empagliflozin, a sodium-glucose co-transporter inhibitor, or a placebo. All-cause mortality in both empagliflozin groups was 3.7% compared to 5.9% in the placebo group, with a number needed to treat of 38 to reduce mortality over a 3.3 year period. Interestingly, there was no difference between the empagliflozin groups and the placebo group regarding rates of heart attack or stroke, so it's unclear as yet just what is responsible for that mortality benefit. There was no difference in efficacy between the two doses, but the higher dose caused more adverse events. In the AFP POEM, Dr. Ebell points out that generalizing this finding to patients with type 2 diabetes who do not have CVD is not appropriate.
Of the other medications shown to lower mortality in type 2 diabetes, metformin may be the best known. Metformin has a proven mortality benefit for all patients with type 2 diabetes, even those patients on insulin. Metformin is so beneficial that a recent AFP article recaps recommendations to only consider discontinuing it if a patient's GFR is less than 44 mL/min, not necessarily just because the creatinine is > 1.5 in men or >1.4 in women as previously thought.
Ramipril and the combo of perindopril and indapamide have been specifically shown to help type 2 diabetics live longer, and a 2014 meta-analysis suggests this benefit is a generalizable to the entire ACE inhibitor class. Also, ACE inhibitors have a clear mortality benefit in diabetics who have diabetic nephropathy, though only at maximum tolerated doses and not so-called lower "renal protective" doses.
While hypertension control helps diabetics live longer, over-control may be harmful. A recent meta-analysis found that lowering systolic blood pressure in type 2 diabetics already at or below 140 mmHg was associated with an increased risk of mortality. This meta-analysis calls into question the common practice of prescribing those low "renal protective" doses of ACE inhibitors to type 2 diabetics with systolic blood pressures (SBPs) <140 and normal renal function.
Certainly, other medications may help lower morbidity and improve quality of life in patients with type 2 diabetes; to read more about diabetes treatment check out the AFP By Topic on Diabetes: Type 2 which includes this 2016 Practice Guideline on Preventing CVD in Adults with Type 2 Diabetes Mellitus. Diabetes also figures prominently in some of AFP's newer features, including this recent Medicine by the Numbers article on glycemic control goals and the January 15, 2016 AFP podcast.