Incretin-based therapies in patients with Type 2 diabetes mellitus and renal impairment

Howse, Patricia Marie (2023) Incretin-based therapies in patients with Type 2 diabetes mellitus and renal impairment. Masters thesis, Memorial University of Newfoundland.

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Abstract

The objective of this thesis is to add to literature addressing the safety and effectiveness of incretin-based agents in patients with diabetes and chronic kidney disease. Methods: Two complementary studies were conducted, a systematic review and meta-analysis and a population-based cohort study. Results: The systematic review and meta-analysis demonstrated in patients with diabetes and moderate or severe chronic kidney disease (CKD), incretin-based therapies effectively reduced glycated hemoglobin compared to placebo (WMD -0.53; 95%CI -0.64, -0.42). The pooled relative risk (RR) for all-cause mortality indicated no evidence of effect for incretin vs. placebo (RR 1.02; 95%CI 0.50, 2.06). In the cohort study dipeptidyl peptidase-4 (DPP-4) inhibitors, as second-line therapy were not significantly associated with a reduction in all-cause mortality (adjusted hazard ratio 0.74 [95%CI 0.52-1.04] vs. SU initiators). Conclusion: The meta-analysis supports incretin-based therapies as effectively reducing glycemia without substantial increased risk of hypoglycemia. The cohort study demonstrated second-line DPP4 inhibitor therapy was not significantly associated with a reduction in all-cause mortality when compared to sulfonylureas. Despite their introduction to the pharmaceutical market in 2007, there is still much to be understood regarding incretin therapy.

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