Exenatide was the most effective single-drug treatment for type 2 diabetes in rats, but combining it with empagliflozin and quercetin produced the best overall improvements in blood sugar, insulin resistance, and cholesterol.
Triple combo uniquely reduced insulin resistanceOnly the combination of exenatide + empagliflozin + quercetin significantly decreased HOMA-IR and leptin levels, effects that no single drug achieved alone
What the researchers found
In type 2 diabetic rats, the GLP-1 agonist exenatide showed more pronounced antidiabetic effects than either empagliflozin (an SGLT2 inhibitor) or quercetin (a plant flavonoid) when used alone. However, the triple combination of all three drugs produced the best overall results.
All treatments lowered glucose, HbA1c, and triglyceride levels. Exenatide and the combination therapy were the only treatments to increase insulin levels. The combination was uniquely effective at decreasing leptin levels and HOMA-IR (insulin resistance). Exenatide improved HDL cholesterol and LDL levels, while the combination therapy showed the strongest combined antidiabetic and lipid-lowering effects.
Why it matters
Type 2 diabetes management often requires multiple drugs with complementary mechanisms. This study systematically compared a peptide drug (exenatide), a newer oral drug (empagliflozin), and a natural compound (quercetin) both alone and in combination. The finding that exenatide outperformed the others as monotherapy reinforces GLP-1 agonists' strong position in diabetes treatment. The superior results from triple combination therapy suggest that adding quercetin as a supplement alongside prescription medications could enhance metabolic outcomes.
The numbers in context
n=67 rats · 7 groups · exenatide 10 μg/kg · empagliflozin 50 mg/kg · quercetin 50 mg/kg · 8-week treatment · all treatments ↓ glucose and HbA1c · combination uniquely ↓ HOMA-IR and leptin · exenatide ↑ HDL
How the study worked
67 Wistar Albino male rats were divided into seven groups: healthy control, diabetes control, diabetes + sham, and four treatment groups (exenatide, empagliflozin, quercetin, and triple combination). Diabetes was induced and treatments were administered for 8 weeks. Outcomes measured included blood glucose, HbA1c, insulin, adiponectin, leptin, total antioxidant levels, LDL, HDL, triglycerides, HOMA-IR (insulin resistance), and HOMA-β (beta cell function).
Who was studied
67 Wistar Albino male rats with induced type 2 diabetes, divided into 7 groups
What this study cannot tell us
This is an animal study in rats with chemically induced diabetes, which may not fully replicate human type 2 diabetes. The drug doses were selected for rats and may not translate directly to human dosing. The 8-week treatment period is relatively short for assessing chronic diabetes management. The study does not report on potential drug interactions or adverse effects. Sample sizes per group (~9-10 rats) are small.
How to read the evidence
This study is graded as preliminary because it was conducted in rats with chemically induced diabetes. While the comparison design is informative, no human data supports these specific combination findings yet.
When this study was published
Published in 2024, this is a recent study relevant to current combination therapy strategies for type 2 diabetes.
The bigger picture
Combination therapy is becoming the standard of care for type 2 diabetes, and this study supports that trend at the preclinical level. The inclusion of quercetin — a naturally occurring flavonoid found in onions, apples, and berries — alongside two prescription drugs is noteworthy because it suggests that dietary supplements could meaningfully complement pharmaceutical therapy. As GLP-1 agonists become increasingly dominant in diabetes and obesity management, understanding how they synergize with other drug classes remains an active research priority.
Questions still open
- Would the triple combination of exenatide, empagliflozin, and quercetin show the same synergistic benefits in human clinical trials?
- Could quercetin supplementation meaningfully enhance outcomes for patients already on GLP-1 agonist and SGLT2 inhibitor therapy?
- How do the long-term safety profiles of these three drugs interact when used in combination?
Common questions
What is exenatide and how is it different from semaglutide?
Can I add quercetin to my diabetes medication?
Read the original research
The comparison of the antidiabetic effects of exenatide, empagliflozin, quercetin, and combination of the drugs in type 2 diabetic rats.
Fundamental & clinical pharmacology, 38(3), 511-522
Citation
Korkmaz, Yasemin; Dik, Burak. (2024). The comparison of the antidiabetic effects of exenatide, empagliflozin, quercetin, and combination of the drugs in type 2 diabetic rats.. Fundamental & clinical pharmacology, 38(3), 511-522. https://doi.org/10.1111/fcp.12975