Table 5.
Findings of the GRADE analysis
| Combination of SGLT2i and GLP-1RA therapy compared to SGLT2i or GLP-1RA therapy for type 2 diabetes |
|
Patient or population: T2DM Interventiona: Combination of SGLT2i and GLP-1RA therapy Comparisona: SGLT2i or GLP-1RA therapy |
| Outcome | Anticipated absolute effects (95% CI) | Relative effect (95% CI) | No. of participants (studies) | Certainty of the evidence (GRADE) | Comments |
|---|---|---|---|---|---|
| Risk with combination of SGLT2i and GLP-1RA therapy | |||||
| All-cause mortality | 22 per 1000 (19 to 27) | RR 0.49 (0.41 to 0.60) | 4,18,630 (2 observational studies) |
⨁⨁◯◯ Low |
Combination of SGLT2i and GLP-1RA therapy may result in a large reduction in all-cause mortality due to T2DM |
|
Change in HbA1c Follow-up: 6 months |
MD 1.48 lower (1.75 lower to 1.21 lower) | – | 1011 (7 observational studies) |
⨁⨁◯◯ Low |
Combination of SGLT2i and GLP-1RA therapy may result in a slight (but important) reduction in HbA1C |
|
Change in FPG Follow-up: 6 months |
MD 2.27 lower (2.78 lower to 1.76 lower) | – | 945 (5 observational studies) |
⨁◯◯◯ Very low |
Combination of SGLT2i and GLP-1RA therapy may reduce FPG but the evidence is very uncertain |
|
Change in BMI Follow-up: mean 6 months |
MD 1.71 lower (2.74 lower to 0.67 lower) | – | 850 (4 observational studies) |
⨁⨁◯◯ Low |
The combination of SGLT2i and GLP-1RA therapy may reduce BMI |
|
Change in SBP Follow-up: 6 months |
MD 6.35 lower (10.17 lower to 2.53 lower) | – | 859 (5 observational studies) |
⨁⨁◯◯ Low |
Evidence suggests that the combination of SGLT2i and GLP-1RA therapy results in a large reduction in SBP |
|
Change in eGFR Follow-up: 6 months |
MD 1.04 lower (4.56 lower to 2.49 higher) | – | 312 (2 observational studies) |
⨁⨁◯◯ Low |
The combination of SGLT2i and GLP-1RA therapy may reduce eGFR |
|
Change in total cholesterol Follow-up: 6 months |
MD 0.11 lower (0.25 lower to 0.02 higher) | – | 698 (3 observational studies) |
⨁⨁◯◯ Low |
The combination of SGLT2i and GLP-1RA therapy may reduce total cholesterol |
BMI Body mass index, CI confidence interval, eGFR estimated glomerular filtration rate, FPG fasting plasma glucose, GLP-1RA glucagon-like peptide-1 receptor agonist, GRADE Grading of Recommendations, Assessment, Development and Evaluation, HbA1c glycated hemoglobin, MD mean difference, RR relative risk, SBP systolic blood pressure, SD standard deviation, SGLT2i sodium–glucose transport protein 2 inhibitor, T2DM type 2 diabetes mellitus
aIntervention and comparator for changes in HbA1c, FPG, BMI, SBP, eGFR, and total cholesterol was the combination of SGLT2i + GLP-1RA administered simultaneously, but MD was calculated based on the difference in the parameters between baseline and follow-up at 6 months