Newer glucose-lowering drugs associated with lower mortality risk than insulin

Researchers compared Swedish patients with type 2 diabetes who were new users of dipeptidyl peptidase-4 inhibitors or sodium-glucose cotransporter-2 inhibitors with patients initiating insulin.


Compared to insulin, newer oral glucose-lowering drugs were associated with lower risks of all-cause mortality, cardiovascular disease (CVD), and severe hypoglycemia in a recent study.

Using Swedish registries, researchers identified patients with type 2 diabetes who, during 2013 and 2014, were new users of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT2) inhibitors (only dapagliflozin was available in Sweden at the time). They used patients initiating insulin as a comparator group and matched groups using propensity scoring.

Researchers matched 21,758 patients (10,879 on newer drugs, 10,879 on insulin) and followed them for a median of about 1.5 years. The three endpoints were death from any cause; fatal or nonfatal CVD (a main inpatient diagnosis of myocardial infarction, ischemic stroke, unstable angina pectoris, heart failure, or cardiovascular death); and severe hypoglycemia (a main or secondary inpatient diagnosis of hypoglycemia or diabetes with coma). Results of the industry-funded study were published online on March 16 by Diabetes, Obesity and Metabolism.

In the drug group, incidence per 100 patient-years of all-cause mortality, CVD, and severe hypoglycemia were 2.56, 4.66, and 0.12, respectively. In the insulin group, these figures were 4.57, 5.49, and 0.46 per 100 patient-years, respectively. Compared to the insulin group, the drug group had a 44% lower risk of all-cause mortality, a 15% lower risk of cardiovascular disease, and 74% lower risk of severe hypoglycemia. In patients with established CVD at baseline, treatment with the novel drugs was associated with a lower risk of all-cause mortality than treatment with insulin. Those without CVD at baseline saw lower risks of all three outcomes (all-cause mortality, CVD, and severe hypoglycemia) with drug treatment versus insulin treatment.

In a separate analysis, researchers compared propensity-matched patients taking dapagliflozin (n=2,047) versus insulin (n=4,094) and DPP-4 inhibitors (n=10,279) versus insulin (n=10,279). Compared to insulin, dapagliflozin use was associated with a 56% lower risk of all-cause mortality (P<0.001) and a 49% lower risk of CVD (P=0.011) but no difference in severe hypoglycemia. DPP-4 inhibitors showed a significantly reduced risk of all-cause mortality and severe hypoglycemia compared to insulin (41% [P<0.001] and 69% [P=0.002], respectively), but no difference in CVD.

The authors noted the inherent limitations of an observational study, such as the potential for unmeasured confounders, lack of information on diabetes duration and body weight, and the inability to compare dapagliflozin to other SGLT2 inhibitors. In addition, they noted that their assessment of hypoglycemia was “crude” and included only events that led to hospital admission (the number of hypoglycemia events was low in the dapagliflozin-only group, which limited statistical interpretation).