Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis.

Mearns ES, Sobieraj DM, White CM, Saulsberry WJ, Kohn CG, Doleh Y, Zaccaro E, Coleman CI

PloS one28 Apr 2015Cited by 112 (Europe PMC)

PMID25919293PMCIDPMC4412636DOI10.1371/journal.pone.0125879PepBankPUB-25919293

Summary

IntroductionWhen first line therapy with metformin is insufficient for patients with type 2 diabetes (T2D), the optimal adjunctive therapy is unclear. We assessed the efficacy and safety of adjunctive antidiabetic agents in patients with inadequately controlled T2D on metformin alone.Materials and methodsA search of MEDLINE and CENTRAL, clinicaltrials.gov, regulatory websites was performed. We included randomized controlled trials of 3-12 months duration, evaluating Food and Drug Administration or European Union approved agents (noninsulin and long acting, once daily basal insulins) in patients experiencing inadequate glycemic control with metformin monotherapy (≥ 1500 mg daily or maximally tolerated dose for ≥ 4 weeks). Random-effects network meta-analyses were used to compare the weighted mean difference for changes from baseline in HbA1c, body weight (BW) and systolic blood pressure (SBP), and the risk of developing hypoglycemia, urinary (UTI) and genital tract infection (GTI).ResultsSixty-two trials evaluating 25 agents were included. All agents significantly reduced HbA1c vs. placebo; albeit not to the same extent (range, 0.43% for miglitol to 1.29% for glibenclamide). Glargine, sulfonylureas (SUs) and nateglinide were associated with increased hypoglycemia risk vs. placebo (range, 4.00-11.67). Sodium glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 analogs, miglitol and empagliflozin/linagliptin significantly reduced BW (range, 1.15-2.26 kg) whereas SUs, thiazolindinediones, glargine and alogliptin/pioglitazone caused weight gain (range, 1.19-2.44 kg). SGLT2 inhibitors, empagliflozin/linagliptin, liraglutide and sitagliptin decreased SBP (range, 1.88-5.43 mmHg). No therapy increased UTI risk vs. placebo; however, SGLT2 inhibitors were associated with an increased risk of GTI (range, 2.16-8.03).ConclusionsAdding different AHAs to metformin was associated with varying effects on HbA1c, BW, SBP, hypoglycemia, UTI and GTI which should impact clinician choice when selecting adjunctive therapy.

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

Results from this study2

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone2

In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Liraglutide.

01HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes on metformin, SGLT2 inhibitors, empagliflozin/linagliptin, liraglutide and sitagliptin decreased systolic blood pressure (range, 1.88-5.43 mmHg); the range pools these agents.
In plain wordsIn adults with type 2 diabetes on metformin, several add-on drugs, liraglutide among them, lowered systolic blood pressure; the range covers all of them.
Peptide
Liraglutide
Outcome
DecreaseSystolic blood pressure, pooled range for named agents including liraglutide
Study
n: not reported in source
Outcome group
Blood pressure · Cardiovascular
Measurements
Systolic blood pressure decrease
1.88 to 5.43 mmHg
SGLT2 inhibitors, empagliflozin/linagliptin, liraglutide, sitagliptin
Source sentences
Summary
SGLT2 inhibitors, empagliflozin/linagliptin, liraglutide and sitagliptin decreased SBP (range, 1.88-5.43 mmHg).
1 context sentence(design, population, supporting numbers)
Summary · context
We included randomized controlled trials of 3-12 months duration, evaluating Food and Drug Administration or European Union approved agents (noninsulin and long acting, once daily basal insulins) in patients experiencing inadequate glycemic control with metformin monotherapy (≥ 1500 mg daily or maximally tolerated dose for ≥ 4 weeks).
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-2591929301
02HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes on metformin, SGLT2 inhibitors, GLP-1 analogs, miglitol and empagliflozin/linagliptin significantly reduced body weight (range, 1.15-2.26 kg); the class is pooled.
In plain wordsIn adults with type 2 diabetes on metformin, GLP-1 drugs as a class, with other drugs, reduced body weight; none is given for liraglutide alone.
Peptide
Liraglutide
Outcome
DecreaseBody weight, GLP-1 analogs pooled with other agents
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Measurements
Body weight reduction
1.15 to 2.26 kg
SGLT2 inhibitors, GLP-1 analogs, miglitol, empagliflozin/linagliptin
Source sentences
Summary
Sodium glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 analogs, miglitol and empagliflozin/linagliptin significantly reduced BW (range, 1.15-2.26 kg)
1 context sentence(design, population, supporting numbers)
Summary · context
We included randomized controlled trials of 3-12 months duration, evaluating Food and Drug Administration or European Union approved agents (noninsulin and long acting, once daily basal insulins) in patients experiencing inadequate glycemic control with metformin monotherapy (≥ 1500 mg daily or maximally tolerated dose for ≥ 4 weeks).
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-2591929302

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Version 2Current
12 Oct 2026, 12:10 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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