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Review
. 2024 Nov 25;16(11):e74400.
doi: 10.7759/cureus.74400. eCollection 2024 Nov.

Comparing the Efficacy and Long-Term Outcomes of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors, Dipeptidyl Peptidase-4 (DPP-4) Inhibitors, Metformin, and Insulin in the Management of Type 2 Diabetes Mellitus

Farhan Khan  1 , Tanjil Hussain  2 , Taha Zahid Chaudhry  3 , Fnu Payal  4 , Abdullah Shehryar  5 , Abdur Rehman  6 , Afif Ramadhan  7 , Muhammad Tassaduq Hayat  8   9 , Muath M Dabas  10 , Mustafa Khan  11
Affiliations
Review

Comparing the Efficacy and Long-Term Outcomes of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors, Dipeptidyl Peptidase-4 (DPP-4) Inhibitors, Metformin, and Insulin in the Management of Type 2 Diabetes Mellitus

Farhan Khan et al. Cureus. .

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance, and decreased insulin secretion. With its rising global prevalence, effective management strategies are critical to reducing morbidity and mortality. This systematic review compares the efficacy, safety, and long-term outcomes of four major pharmacological treatments for T2DM: sodium-glucose cotransporter-2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, and insulin. We focused on randomized controlled trials (RCTs) published within the last five years (2019-2024) to provide an up-to-date assessment of glycemic control, cardiovascular and renal benefits, weight effects, and the risk of hypoglycemia. The review highlights that while all four medication classes effectively reduce HbA1c levels, SGLT2 inhibitors stand out for their additional cardiovascular and renal benefits, including significant reductions in major adverse cardiovascular events and chronic kidney disease progression. Metformin remains a cornerstone first-line therapy due to its safety, efficacy, and affordability. DPP-4 inhibitors are a weight-neutral, well-tolerated option, although their efficacy may diminish over time. Insulin, while the most potent glucose-lowering agent, carries a higher risk of hypoglycemia and weight gain. Our findings emphasize the importance of personalized, patient-centered approaches that account for the distinct therapeutic profiles of these treatments. Future research should prioritize head-to-head comparisons and optimal therapy sequencing to refine treatment guidelines for diverse patient populations.

Keywords: cardiovascular outcomes; dpp-4 inhibitors; glycemic control; hypoglycemia risk; insulin; metformin; renal protection; sglt2 inhibitors; type 2 diabetes mellitus; weight changes.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. The PRISMA flowchart represents the study selection process.
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
See this image and copyright information in PMC

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