Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.

Shi Q, Nong K, Vandvik PO, Guyatt GH, Schnell O, Rydén L, Marx N, Brosius FC 3rd, Mustafa RA, Agarwal A, Zou X, Mao Y and 28 more

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Asadollahifar A, Chowdhury SR, Zhai C, Gupta S, Gao Y, Lima JP, Numata K, Qiao Z, Fan Q, Yang Q, Jin Y, Ge L, Yang Q, Zhu H, Yang F, Chen Z, Lu X, He S, Chen X, Lyu X, An X, Chen Y, Hao Q, Standl E, Siemieniuk R, Agoritsas T, Tian H, Li S

BMJ (Clinical research ed.)6 Apr 2023Cited by 204 (Europe PMC)

PMID37024129PMCIDPMC10077111DOI10.1136/bmj-2022-074068PepBankPUB-37024129

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Summary

ObjectiveTo compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options.DesignSystematic review and network meta-analysis.Data sourcesOvid Medline, Embase, and Cochrane Central up to 14 October 2022.Eligibility criteria for selecting studiesEligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach.ResultsThe analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes).ConclusionsThis network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes.Systematic review registrationPROSPERO CRD42022325948.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. 3 results from people.

01HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes, a network meta-analysis found that tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty).
In plain wordsIn adults with type 2 diabetes, tirzepatide probably reduced body weight more than any other drug in this network analysis.
Peptide
Tirzepatide
Outcome
DecreaseBody weight (mean difference)
Study
n: not reported in source
Comparator
Standard treatments
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
Mean difference in body weight
−8.57 kg
tirzepatide vs standard treatments
Source sentences
Summary
Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty).
1 context sentence(design, population, supporting numbers)
Summary · context
The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments.
Show in the study text Report a problemFND-3702412901
02HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes, a network meta-analysis found that tirzepatide probably improves quality of life.
In plain wordsIn adults with type 2 diabetes, tirzepatide probably improved quality of life in this network analysis.
Peptide
Tirzepatide
Outcome
IncreaseQuality of life
Study
n: not reported in source
Comparator
Standard treatments
Outcome group
Quality of life · Whole body
Studied dose
Dose not stated
Source sentences
Summary
GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life.
1 context sentence(design, population, supporting numbers)
Summary · context
The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments.
Show in the study text Report a problemFND-3702412902
03HumanSystematic reviewSafety outcome
In adults with type 2 diabetes, a network meta-analysis reported severe gastrointestinal adverse events with tirzepatide.
In plain wordsIn adults with type 2 diabetes, this network analysis linked tirzepatide to severe stomach and gut side effects.
Peptide
Tirzepatide
Outcome
IncreaseSevere gastrointestinal adverse events
Study
n: not reported in source
Comparator
Standard treatments
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone).
1 context sentence(design, population, supporting numbers)
Summary · context
The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments.
Show in the study text Report a problemFND-3702412903

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Version 2Current
12 Oct 2026, 12:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

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