Adults with type 2 diabetes, mild renal insufficiency and an elevated HbA1c assigned the DPP-IV inhibitor sitagliptin experienced greater improvements in glycemic profile vs. similar patients assigned the SGLT2 inhibitor dapagliflozin, according to findings from the ComposIT-R study.
“While it is widely recognized that the choice of an antihyperglycemic agent for treatment of type 2 diabetes should be influenced by renal function, only [chronic kidney disease] stages 3 to 5 are usually considered relevant to that decision,” Russell Scott, MD, PhD, of the Lipid and Diabetes Research Group at Christchurch School of Medicine, Christchurch, New Zealand, and colleagues wrote in the study background. “Additionally, clinical studies in patients with CKD are usually focused on patients with [estimated glomerular filtration rate of] < 60 mL/min/1.73m2. While patients with type 2 diabetes and mild renal insufficiency are typically included in phase 3 studies of antihyperglycemic therapies, the specific impact of mild renal insufficiency on the efficacy and safety of most [antihyperglycemic agents] has not generally been prospectively evaluated in clinical trials.”
In a multinational, randomized, double-blind, active-comparator-controlled, parallel-group trial, researchers evaluated adults with type 2 diabetes and mild renal insufficiency, defined as an eGFR between 60 mL/min/1.73m² and 90 mL/min/1.73m², at 185 sites in 24 countries (mean age, 67 years; 42% women; mean BMI, 31.6 kg/m²; mean HbA1c, 7.7%; mean diabetes duration, 10.6 years). Participants had an HbA1c of between 7% and 9.5% and fasting glucose between 6.1 mmol/L and 14.4 mmol/L at baseline.
Researchers randomly assigned participants to 100 mg sitagliptin once daily (n=307; Januvia, Merck) or 5 mg dapagliflozin (Farxiga, AstraZeneca), adjusted to 10 mg, once daily for 24 weeks.
Efficacy endpoints included change from baseline in HbA1c, 2-hour post-prandial glucose, fasting plasma glucose, post-prandial insulin, post-prandial glucagon and insulin to glucagon ratio at 24 weeks.
At 24 weeks, the sitagliptin group experienced a greater least-squares mean HbA1c change from baseline vs. the dapagliflozin group (least squares mean, –0.51% [95% CI, –0.6 to –0.43] vs. least squares mean, –0.36% [95% CI, –0.45 to –0.27]). There was a between-group difference of –0.15 (95% CI, –0.26 to –0.04)
Both treatment groups showed a near maximum decrease in Hba1c by week 10, according to the researchers. At week 24, the between group difference in the percentage of patients with an HbA1c of less than 7% was 15.5 (95% CI, 7.7-23.2).
One or more adverse events occurred in 48.9% of the sitagliptin group vs. 51.6% in the dapagliflozin group. There were no deaths. Summary measures of adverse events were comparable between groups, apart from drug-related adverse events, according to researchers (7.8% in the sitagliptin group vs. 13.7% in the dapagliflozin group; between-group difference –5.9 [95% CI, –11 to –1]).
A pre-specified analysis found no significant between-group difference in 2-hour incremental post-prandial glucose excursion.
“In patients with type 2 diabetes and mild renal insufficiency who were inadequately controlled on metformin ± sulfonylurea, treatment with sitagliptin compared with dapagliflozin demonstrated greater glycemic efficacy, a greater percentage of patients at glycemic goal, and a good safety profile. Additional prospective studies, evaluating the safety and efficacy of other [antihyperglycemic agents] in patients with mild renal impairment, could be of value to prescribing physicians.” – by Jennifer Byrne
Disclosure: The authors report no relevant financial disclosures.