October 14, 2020

Sitagliptin versus intermediate-acting insulin for type 2 diabetes

Query 11-04b: What is the comparative effectiveness and safety of sitagliptin and NPH insulin for the management of type 2 diabetes not controlled by metformin plus sulfonylurea?

This research was funded by the Drug Safety and Effectiveness Network (DSEN) and conducted by the following investigators: Cristiano Moura, Sasha Bernatsky, Michal Abrahamowicz, Louise Pilote and the CAN-AIM Team.

Issue:

  • Most guidelines suggest metformin as initial therapy in type 2 diabetes mellitus (DM), and sulfonylurea is commonly used as second-line therapy. 
  • However, most type 2 DM people eventually need additional treatment to achieve glycemic control.

Study aim:

  • To compare DPP-4 inhibitors (sitagliptin) with insulin neutral protamine haegadorn (NPH insulin) in terms of effectiveness and safety for the management of patients with type 2 diabetes mellitus (T2DM) not controlled by metformin and sulfonylureas.

Study description:

  • CAN-AIM conducted two longitudinal analyses from international databases.
  • CAN-AIM investigators conducted a comparison between DPP-4 and NPH insulin in terms of glycated hemoglobin (HbA1C) levels, body mass index (BMI), therapy persistence, hypoglycemia, and cardiovascular outcomes (myocardial infarction, unstable angina, coronary artery bypass graft, coronary revascularization, or percutaneous coronary intervention).

Study findings:

  • Sitagliptin was associated with a significant reduction in BMI (one-unit reduction measured after 1 year) compared to NPH insulin. No clinically significant difference in HbA1C levels between the two groups.
  • Initiators of NPH insulin discontinued earlier and have a three times higher risk of hypoglycemia when compared to initiators of DPP-4.
  • The risk of cardiovascular outcomes was similar across groups.

Summary:

  • Our results bring evidence from the real-world population and support prior findings that DPP-4 effectively treats type 2 DM. Considering the lower risk of hypoglycemia, DPP-4 should be preferred instead of NPH insulin as third-line therapy for patients not controlled with metformin plus sulfonylurea.
  • Type 2 diabetes mellitus patients initiating on DPP-4 as third-line therapy are more likely to persist on therapy, have a greater improvement on BMI, and lower risk of hypoglycemia than initiators of NPH insulin.

The final analysis using Marketscan for this query was finalized. With T2DM analysis, we found that NPH insulin initiators discontinued earlier and have a three times higher risk of hypoglycemia compared to DPP-4 users.

Moura et al. Treatment discontinuation and clinical events in type 2 diabetes patients treated with dipeptidyl peptidase-4 inhibitors or NPH insulin as third-line therapy. Journal of Diabetes Research, 2018: 4817178.

Elharram M et al. Novel glucose-lowering agents are associated with a lower risk of cardiovascular and adverse events in type-2 diabetes: a population-based analysis. (Manuscript in preparation)

Raparelli V et al. Sex differences in effectiveness of glucose-lowering drugs in type-2 diabetics requiring second-line agents. (Manuscript in preparation)

Moura et al. Treatment discontinuation and rates of hypoglycemia in type 2 diabetes patients treated with dipeptidyl peptidase-4 (DDP4) inhibitors or NPH insulin as third-line therapy. 2016 (ICPE abstract)

Elharram M et al. Novel glucose-lowering agents are associated with a lower risk of cardiovascular and adverse events in type-2 diabetes: a population-based analysis. Abstract – Moderated Presentation. Canadian Cardiovascular Congress (CCC), Toronto, Ontario, October 20-23, 2018.

Elharram M et al. Risk of cardiovascular events in type-2 diabetes patients initiating novel glucose lowering drugs: a population-based analysis. Oral Presentation. McGill Cardiovascular Research Day, Jewish General Hospital, Montreal, Quebec, May 2, 2018.

For more information, contact: Autumn Neville, Research Coordinator. [email protected]