GLP-1 receptor agonists + SGLT2 inhibitors has been studied in 37 papers since 2018: 26 observational studies in people, 10 reviews; 26 in the past year. The newest story, Nov 7, 2026: “Diabetes drug combination linked to fewer limb complications”.
Human studies associate combined GLP-1 receptor agonists and SGLT2 inhibitors with lower mortality, including a preprint in type 2 diabetes with COPD. One study finds no atrial fibrillation reduction versus SGLT2 inhibitors alone; a review describes lower myocardial infarction and stroke risks versus monotherapy.
89 findings in 32 papers from 2018 to 2026, 15 of them since July 2026
Independent labs found the same change in people. 27 independent labs in 12 countries.
“Hemoglobin A1c (HbA1c) levels were significantly reduced (mean difference [MD] -0.26; 95% confidence interval [CI] -0.32, -0.20; P < 0.0001)”
Humans: replicated by independent labs. Cells, worms or flies and mice: nothing yet.
C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.
Labs are independent when their papers share no last author and no institution.
Against: findings that point the other way from most findings on the same outcome.
Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.
27 independent labs in 12 countries
10 findings against
Funders: AstraZeneca and 7 more
3 of 78 findings with company ties
Humans26
Studies in people
2 studies gave GLP-1 receptor agonists + SGLT2 inhibitors to people and measured what changed.
↑up: Increases estimated glomerular filtration rateMD 2.18 (95% CI 1.56 to 2.80)
↓down: Decreases LDL cholesterolMD -0.56 (95% CI -0.64 to -0.48)
Review of trials
11,679 people pooledelderlyOlder adults; Patient cohorts
American journal of translational research, Nov 15, 2024
What did studies of GLP-1 receptor agonists + SGLT2 inhibitors find?
25
Studies of GLP-1 receptor agonists + SGLT2 inhibitors measured 25 outcomes; the most studied are major adverse cardiovascular events (4 studies), HbA1c (3) and stroke (2).
Major adverse cardiovascular events
↔no changein humans3↓downin humans1RR 0.83
4 studies
GLP-1 receptor agonists + SGLT2 inhibitors decrease major adverse cardiovascular events in humans (versus SGLT2 inhibitors alone) (RR 0.83, 95% CI 0.72-0.96).
“combined use was associated with lower MACE (RR 0.83, 95% CI 0.72-0.96) and HHF (RR 0.73, 95% CI 0.56-0.94) than SGLT2i alone”
GLP-1 receptor agonists + SGLT2 inhibitors were not clearly linked with major adverse cardiovascular events in humans (Type 2 diabetes and HFpEF; compared with GLP-1 monotherapy) (16.57% vs. 16.40%; p = 0.840).
“The incidence of major adverse cardiovascular events (16.57% vs. 16.40%; p = 0.840) and stroke (6.46% vs. 6.63%; p = 0.332) was similar between the two groups.”
HumansType 2 diabetes and HFpEF; compared with GLP-1 monotherapy
GLP-1 receptor agonists + SGLT2 inhibitors were not clearly linked with major adverse cardiovascular events in humans (Chronic kidney disease; compared with SGLT2i monotherapy) (aHR 0.88, 95% CI 0.70–1.11; p = 0.29).
“There was no significant reduction in risk of MACE (aHR, 0.88; 95% CI, 0.70-1.11; p = 0.29).”
HumansChronic kidney disease; compared with SGLT2i monotherapy6 months to 2 years after treatment initiation
GLP-1 receptor agonists + SGLT2 inhibitors showed no clear effect on major adverse cardiovascular events in humans (cardiovascular outcome trials; synergistic or additive protection).
“cardiovascular outcome trials (CVOTs) have not demonstrated a synergistic or additive protective effect of combined therapy on MACE or renal endpoints.”
Reviewcardiovascular outcome trials; synergistic or additive protection
GLP-1 receptor agonists + SGLT2 inhibitors are linked with lower HbA1c in humans (combined therapy compared with standard treatment) (median change -2% vs -1%).
“Glycaemic outcomes showed greater improvement in the GLP-1RA/SGLT2-i therapy (median change:-2% VS -1%; p=0.001) in 18 months.”
Humanscombined therapy compared with standard treatment18 monthsn = 199
“Evidence suggests that combining SGLT-2 inhibitors and GLP-1 receptor agonists improves metabolic outcomes, including HbA1c, body weight, and blood pressure.”
GLP-1 receptor agonists + SGLT2 inhibitors were not clearly linked with stroke in humans (Type 2 diabetes and HFpEF; compared with GLP-1 monotherapy) (6.46% vs. 6.63%; p = 0.332).
“The incidence of major adverse cardiovascular events (16.57% vs. 16.40%; p = 0.840) and stroke (6.46% vs. 6.63%; p = 0.332) was similar between the two groups.”
HumansType 2 diabetes and HFpEF; compared with GLP-1 monotherapy
GLP-1 receptor agonists + SGLT2 inhibitors were not clearly linked with stroke in humans (heart failure and type 2 diabetes; compared with SGLT2i alone) (1-year RR 0.882 (95% CI 0.767–1.013)).
“No significant increase in stroke risk was observed.”
Humansheart failure and type 2 diabetes; compared with SGLT2i alone1 year
GLP-1 receptor agonists + SGLT2 inhibitors are linked with higher estimated glomerular filtration rate in humans (combination therapy in kidney transplant recipients with type 2 diabetes) (p=0.04).
“Combination therapy showed significant improvements in LDL (p=0.08), eGFR (p=0.04)”
Humanscombination therapy in kidney transplant recipients with type 2 diabeteskidney12 monthsn = 6
GLP-1 receptor agonists + SGLT2 inhibitors are associated with mortality in humans (Peripheral artery disease and type 2 diabetes; compared with neither therapy) (HR 0.23, 95% CI 0.19–0.28).
“lower hazards of MALE (HR, 0.50; 95% CI, 0.33-0.75), major amputation (HR, 0.30; 95% CI, 0.17-0.53), and all-cause mortality (HR, 0.23; 95% CI, 0.19-0.28)”
HumansPeripheral artery disease and type 2 diabetes; compared with neither therapyMedian follow-up 4.42 yearsn = 13,471
GLP-1 receptor agonists + SGLT2 inhibitors are associated with mortality in humans (type 2 diabetes and HFpEF; compared with SGLT2 inhibitor monotherapy) (HR 0.519, 95% CI 0.479–0.562; 48.1% lower hazard).
“the GLP-1RA + SGLT2i combination yielded a 48.1% lower hazard for all-cause mortality (HR: 0.519, 95% CI: 0.479–0.562, p < 0.0001).”
Humanstype 2 diabetes and HFpEF; compared with SGLT2 inhibitor monotherapyone year
GLP-1 receptor agonists + SGLT2 inhibitors are associated with mortality in humans (Type 2 diabetes and HFpEF; compared with GLP-1 monotherapy) (4.35% vs. 5.16%; RR = 0.84).
“Combination therapy (GLP-1 + SGLT2) was associated with a significant decrease in mortality risk compared to GLP-1 monotherapy”
HumansType 2 diabetes and HFpEF; compared with GLP-1 monotherapy
GLP-1 receptor agonists + SGLT2 inhibitors are associated with mortality in humans (Chronic kidney disease; compared with SGLT2i monotherapy) (aHR 0.58, 95% CI 0.40–0.83; p < 0.01).
“initiation of combined SGLT2i and GLP-1RA therapy was associated with lower risks of MAKE and all-cause mortality compared with SGLT2i monotherapy.”
HumansChronic kidney disease; compared with SGLT2i monotherapy6 months to 2 years after treatment initiation
GLP-1 receptor agonists + SGLT2 inhibitors are associated with mortality in humans (Peripheral artery disease and diabetes; compared with neither treatment) (HR 0.23, 95% CI 0.19–0.28).
GLP-1 receptor agonists + SGLT2 inhibitors are linked with a lower risk of mortality in humans (compared with glp-1 receptor agonists alone after catheter ablation) (HR 0.54, 95% CI 0.34-0.87; p=0.01).
“all-cause mortality was lower (HR 0.54, 95% CI 0.34-0.87; p=0.01) in the combination group.”
Humanscompared with glp-1 receptor agonists alone after catheter ablationn = 952
GLP-1 receptor agonists + SGLT2 inhibitors are associated with mortality in humans After transcatheter aortic valve replacement; compared with patients not treated.
“When GLP-1 RA and SGLT2i were combined, there was a decrease in ACM, myocardial infarction, acute heart failure, and arrhythmia after TAVR”
HumansAfter transcatheter aortic valve replacement; compared with patients not treated
GLP-1 receptor agonists + SGLT2 inhibitors are linked with a lower risk of myocardial infarction in humans (compared with monotherapy, random-effects pooled estimate) (HR 0.79, 95% CI 0.70-0.88).
“Combination therapy was associated with a lower overall risk of MI (HR 0.79, 95% CI 0.70-0.88; I2 = 72.8%) and stroke (HR 0.85, 95% CI 0.77-0.93; I2 = 63.5%)”
Humanscompared with monotherapy, random-effects pooled estimate
Diabetes therapy : research, treatment and education of diabetes and related disorders·
GLP-1 receptor agonists + SGLT2 inhibitors are associated with myocardial infarction in humans After transcatheter aortic valve replacement; compared with patients not treated.
“When GLP-1 RA and SGLT2i were combined, there was a decrease in ACM, myocardial infarction, acute heart failure, and arrhythmia after TAVR”
HumansAfter transcatheter aortic valve replacement; compared with patients not treated
GLP-1 receptor agonists + SGLT2 inhibitors are linked with a lower risk of myocardial infarction in humans (adjusted odds compared with non-users) (aOR 0.71 (95% CI 0.64-0.79)).
“the combination group had significantly decreased incidence of MI (aOR 0.71, 95% CI 0.64-0.79)”
GLP-1 receptor agonists + SGLT2 inhibitors are linked with a lower risk of stroke in humans (compared with monotherapy, random-effects pooled estimate) (HR 0.85, 95% CI 0.77-0.93).
“Combination therapy was associated with a lower overall risk of MI (HR 0.79, 95% CI 0.70-0.88; I2 = 72.8%) and stroke (HR 0.85, 95% CI 0.77-0.93; I2 = 63.5%)”
Humanscompared with monotherapy, random-effects pooled estimate
Diabetes therapy : research, treatment and education of diabetes and related disorders·
GLP-1 receptor agonists + SGLT2 inhibitors are linked with a lower risk of stroke in humans (adjusted odds compared with non-users) (aOR 0.76 (95% CI 0.66-0.89)).
“significantly decreased incidence of MI (aOR 0.71, 95% CI 0.64-0.79), stroke (aOR 0.76, 95% CI 0.66-0.89)”
GLP-1 receptor agonists + SGLT2 inhibitors are associated with major adverse cardiovascular events in humans (type 2 diabetes and HFpEF; compared with SGLT2 inhibitor monotherapy) (HR 0.729, 95% CI 0.698–0.762).
“Furthermore, combination therapy resulted in a 27.1% relative risk reduction in MACE (HR: 0.729, 95% CI: 0.698–0.762, p < 0.0001).”
Humanstype 2 diabetes and HFpEF; compared with SGLT2 inhibitor monotherapyone year
GLP-1 receptor agonists + SGLT2 inhibitors lower the risk of major adverse cardiovascular events (as determined by exploratory analysis; statistical superiority criteria not met).
“The glucagon-like peptide-1 receptor agonist (GLP-1 RA) plus sodium-glucose cotransporter 2 inhibitor (SGLT2i) group shows a lower risk of major adverse cardiovascular events (MACE)”
Reviewas determined by exploratory analysis; statistical superiority criteria not met
GLP-1 receptor agonists + SGLT2 inhibitors are associated with major adverse cardiovascular events in humans (real-world evidence in type 2 diabetes mellitus).
“In contrast, real-world evidence suggests incremental benefits across MACE, heart failure, and renal outcomes”
Reviewreal-world evidence in type 2 diabetes mellitus
GLP-1 receptor agonists + SGLT2 inhibitors lower the risk of major adverse cardiovascular events in humans (compared with sglt2 inhibitor monotherapy) (HR 0.56 [0.49–0.64]).
“significantly lower risk of major adverse cardiovascular events (MACE) (HR 0.56 [0.49–0.64], p<0.0001)”
GLP-1 receptor agonists + SGLT2 inhibitors are linked with a lower risk of heart failure in humans (type 2 diabetes) (HR 0.78, 95% CI 0.68-0.89).
“Hazard reductions were also observed for the modified cardiovascular composite (HR 0.81, 95% CI 0.74-0.88) and heart failure (HR 0.78, 95% CI 0.68-0.89).”
Humanstype 2 diabetesmedian follow-up of 1.3 yearsn = 21,664
GLP-1 receptor agonists + SGLT2 inhibitors are associated with major amputation in humans (Peripheral artery disease and type 2 diabetes; compared with neither therapy) (HR 0.30, 95% CI 0.17–0.53).
“combined GLP1-RA/SGLT2 inhibitor therapy was associated with lower hazards of MALE (HR, 0.50; 95% CI, 0.33-0.75), major amputation (HR, 0.30; 95% CI, 0.17-0.53)”
HumansPeripheral artery disease and type 2 diabetes; compared with neither therapyn = 13,471
GLP-1 receptor agonists + SGLT2 inhibitors are associated with major amputation in humans (Peripheral artery disease and diabetes; compared with neither treatment) (HR 0.30, 95% CI 0.17–0.53).
“combined therapy was associated with lower hazards of MALE (HR, 0.50; 95% CI, 0.33–0.75), major amputation (HR, 0.30; 95% CI, 0.17–0.53)”
HumansPeripheral artery disease and diabetes; compared with neither treatment
GLP-1 receptor agonists + SGLT2 inhibitors are associated with major adverse limb events in humans (Peripheral artery disease and type 2 diabetes; compared with neither therapy) (HR 0.50, 95% CI 0.33–0.75).
“Compared with no therapy, combined GLP1-RA/SGLT2 inhibitor therapy was associated with lower hazards of MALE (HR, 0.50; 95% CI, 0.33-0.75)”
HumansPeripheral artery disease and type 2 diabetes; compared with neither therapyMedian follow-up 5.75 yearsn = 13,471
GLP-1 receptor agonists + SGLT2 inhibitors are associated with major adverse limb events in humans (Peripheral artery disease and diabetes; compared with neither treatment) (HR 0.50, 95% CI 0.33–0.75).
“Compared with neither treatment, combined therapy was associated with lower hazards of MALE (HR, 0.50; 95% CI, 0.33–0.75)”
HumansPeripheral artery disease and diabetes; compared with neither treatmentMedian follow-up 5.75 years
GLP-1 receptor agonists + SGLT2 inhibitors are associated with heart failure exacerbations in humans (type 2 diabetes and HFpEF; compared with SGLT2 inhibitor monotherapy) (54.27% versus 57.76%).
“The incidence of heart failure exacerbations was also lower in the dual therapy cohort (54.27%) compared to the monotherapy group (57.76%).”
Humanstype 2 diabetes and HFpEF; compared with SGLT2 inhibitor monotherapyone year
GLP-1 receptor agonists + SGLT2 inhibitors are associated with heart failure exacerbations in humans (Type 2 diabetes and HFpEF; compared with GLP-1 monotherapy) (53.74% vs. 46.31%; RR = 1.16).
“Unexpectedly, the combination therapy cohort had a higher risk of heart failure exacerbations (53.74% vs. 46.31%; RR = 1.16; p = 0.001).”
HumansType 2 diabetes and HFpEF; compared with GLP-1 monotherapy
GLP-1 receptor agonists + SGLT2 inhibitors are associated with acute kidney injury in humans (Type 2 diabetes and HFpEF; compared with GLP-1 monotherapy) (21.15% vs. 18.53%; RR = 1.14).
“An increased risk of developing AKI was observed in the combination therapy cohort compared to monotherapy (21.15% vs. 18.53%; RR = 1.14; p = 0.006).”
HumansType 2 diabetes and HFpEF; compared with GLP-1 monotherapy
GLP-1 receptor agonists + SGLT2 inhibitors are associated with major adverse kidney events in humans (Chronic kidney disease; compared with SGLT2i monotherapy) (aHR 0.62, 95% CI 0.48–0.80; p < 0.01).
“Combined therapy was associated with a lower risk of MAKE”
HumansChronic kidney disease; compared with SGLT2i monotherapy6 months to 2 years after treatment initiation
Combined use was linked to a lower rate of major limb complications over time than use of neither class, with a hazard ratio of 0.50.Combined use was linked to a lower rate of major limb complications over time than use of neither class, with a hazard ratio of 0.50.
Combined use was associated with lower relative rates of serious limb complications and death than neither drug type, with hazard ratios of 0.50 and 0.23.Combined use was associated with lower relative rates of serious limb complications and death than neither drug type, with hazard ratios of 0.50 and 0.23.