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Table 5 Findings of the GRADE analysis

From: Effectiveness and safety of the combination of sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies

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

  1. 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
  2. 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