Comparison of insulin versus established GLP-1 drugs, DPP-4 inhibitors, and SGLT2 inhibitors shows newer drug classes offer comparable glucose control with additional weight and cardiovascular benefits.
Beyond insulinGLP-1 drugs match insulin's glucose control while adding weight loss, heart protection, and kidney benefits that insulin cannot provide
What the researchers found
GLP-1 drugs, DPP-4 inhibitors, and SGLT2 inhibitors provide comparable glucose control to insulin with additional weight, cardiovascular, and kidney benefits.
Why it matters
Insulin was the default add-on for decades. Establishing that newer peptide-based and non-insulin drugs are often superior helps shift prescribing away from insulin-centric approaches.
The numbers in context
Multiple databases searched including Cochrane and PubMed. Compared three drug classes against insulin.
How the study worked
Comparative analysis of insulin versus GLP-1 RA, DPP-4 inhibitors, and SGLT2 inhibitors as add-on therapy in T2D.
Who was studied
Adults with uncontrolled type 2 diabetes requiring treatment intensification
What this study cannot tell us
Some patients still require insulin. T1D and very advanced T2D need insulin regardless. Cost and access to newer drugs vary by healthcare system.
How to read the evidence
Strong evidence: comparative analysis based on extensive clinical trial data for multiple drug classes.
When this study was published
Published in 2025. Reflects the modern treatment hierarchy favoring GLP-1/SGLT2 over insulin.
The bigger picture
The diabetes treatment hierarchy has been inverted. Instead of starting with simple drugs and escalating to insulin, modern guidelines now place GLP-1 drugs and SGLT2 inhibitors before insulin for most patients — a fundamental shift driven by their multi-organ benefits.
Questions still open
- When is insulin still the best choice over GLP-1/SGLT2 drugs?
- Can GLP-1 drugs delay or prevent the need for insulin indefinitely?
- How do combination GLP-1+SGLT2 regimens compare to insulin-based regimens?
Common questions
Should I try GLP-1 drugs before insulin?
When is insulin still necessary?
Read the original research
Insulin Versus Established GLP-1 Receptor Agonists, DPP-4 Inhibitors, and SGLT-2 Inhibitors for Uncontrolled Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Cureus, 17(9), e92175
Citation
Ahmed, Ammar; Tan, Zi; Abd El-Radi, Waddah; Rajamani, Krishnakumar. (2025). Insulin Versus Established GLP-1 Receptor Agonists, DPP-4 Inhibitors, and SGLT-2 Inhibitors for Uncontrolled Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Cureus, 17(9), e92175. https://doi.org/10.7759/cureus.92175