Structured population data were available for 10 of 11 supporting studies. Diabetes type was heterogeneous: 5 studies with type 2 diabetes, 2 studies with type 1 diabetes. 8 studies described adult participants.

3 relevant studies have unresolved authoritative design evidence and do not contribute to design-specific or RoB-specific claims.

3 supporting studies do not have a displayable topic-matched quantitative effect.

Evidence uses heterogeneous comparison contexts: active_comparator, baseline_within_group, placebo, unknown_unresolved, usual_care.

1 supporting study lacks usable structured population information.

4 supporting studies have high, serious, critical, unclear, or unavailable risk-of-bias information.

1 study contains conflicting p-value and significance fields; those significance claims are suppressed.

Source evidence could not be resolved sufficiently for this field.

Not reported in the authoritative source.

Available source content was suppressed because validation identified a conflict.

Not extracted from the authoritative source.

Comparator group

Clinician-reference record is usable with limitations in: population, design, risk_of_bias.

Metformin as first-line therapy, followed by empagliflozin 10 mg as second-line therapy, and tirzepatide 10 mg as third-line therapy.

Intervention group

Metformin as first-line therapy, followed by empagliflozin 10 mg as second-line therapy, and liraglutide 1.8 mg as third-line therapy.

Metformin as first-line therapy, followed by empagliflozin 10 mg as second-line therapy, and semaglutide 1.0 mg as third-line therapy.

Metformin as first-line therapy, followed by empagliflozin 10 mg as second-line therapy, and dulaglutide 3.0 mg as third-line therapy.

Authoritative quality diagnostic: invalid or missing timepoint.

Authoritative quality diagnostic: source evidence unresolved.

Early use of effective therapies may improve diabetes outcomes

Metformin Group

Clinician-reference record is usable with limitations in: design, risk_of_bias.

Patients received semaglutide as part of their treatment regimen.

Semaglutide Group

Patients received either semaglutide, up to 1 mg subcutaneous (sc) weekly, or dulaglutide, up to 1.5 mg sc weekly, as the standard of care in addition to their usual medication regimen.

Patients received dulaglutide as part of their treatment regimen.

Dulaglutide Group

Patients received metformin as the control treatment.

Twenty subjects with T2DM and obesity were started on metformin and a diet and served as the control group.

Authoritative quality diagnostic: invalid or missing unit.

Authoritative quality diagnostic: invalid or missing value.

GLP-1 agonists reduce heart fat thickness in diabetes.

Clinician-reference record is usable with limitations in: comparator.

Patients received insulin glargine in the morning with fixed doses of metformin.

Insulin glargine plus metformin

After 24 weeks, HbA1C levels improved from (mean ± SD) 8.5±0.9% to 7.7±0.8% (69.0±10.0 mmol/mol to 60.8±8.6 mmol/mol) with insulin glargine plus metformin.

Patients received insulin glargine in the morning with fixed doses of glimepiride.

Insulin glargine plus glimepiride

After 24 weeks, HbA1C levels improved from 8.4±1.0% to 7.7±1.3% with insulin glargine plus glimepiride.

Patients received insulin glargine in the morning with fixed doses of both glimepiride and metformin.

Insulin glargine plus glimepiride plus metformin

After 24 weeks, HbA1C levels improved from 8.7±0.9% to 7.3±0.6% with insulin glargine plus glimepiride plus metformin.

Insulin glargine plus metformin and glimepiride improves glycemic control in type 2 diabetes.

Metformin

Empagliflozin

Core clinician-reference fields are available or not applicable.

Participants received a 16-week intermittent fasting plan consisting of 2 nonconsecutive fasting days and 5 days of habitual intake.

5:2 MR

Patients were randomly allocated in a 1:1:1 ratio to receive either metformin, empagliflozin, or 5:2 MR.

Participants received metformin for 16 weeks.

Participants received empagliflozin for 16 weeks.

Intermittent Fasting Diet Improves Glycemic Control in Type 2 Diabetes

Metformin IR 2000 mg

Participants received placebo once daily at the beginning of the morning meal.

Placebo

Participants (T2DM [HbA1c 7–10.5%], eGFR ≥60 mL/min/1.73m, not taking metformin for ≥2 months) were randomized to QD placebo (PBO); QD Metformin DR 600, 900, 1200, or 1500 mg; or to single-blind BID Metformin immediate-release (IR) 1000 mg.

Participants received 600 mg of Metformin delayed-release once daily.

Metformin DR 600 mg

Participants received 900 mg of Metformin delayed-release once daily.

Metformin DR 900 mg

Participants received 1200 mg of Metformin delayed-release once daily.

Metformin DR 1200 mg

Participants received 1500 mg of Metformin delayed-release once daily.

Metformin DR 1500 mg

Participants received 2000 mg of Metformin immediate-release twice daily.

Authoritative quality diagnostic: p value significance conflict.

Metformin DR enhances glycemic control in T2D patients.

Participants received metformin for 3 months followed by a washout period and then switched to placebo for another 3 months.

Participants were randomly assigned in a 1:1 ratio to receive either metformin or placebo for 3 months. Then, after a 1-month washout period (116 half-lives for metformin), the medication was changed to the other treatment for another 3 months.

Participants received placebo for 3 months followed by a washout period and then switched to metformin for another 3 months.

Metformin improves glycemic control in heart failure patients

Placebo Group

Participants received adjunctive metformin at a dose of 1000 mg daily for 9 months.

The metformin group consisted of 15 subjects (8 m/ 7f), of age 15.0 ± 2.5 y.

Participants received similar-appearing placebo capsules daily for 9 months.

The control group was made up of 13 subjects (5m/ 8f), of age 14.5 ± 3.1y.

Authoritative quality diagnostic: age group conflict.

Metformin may improve glycemic control in youth with type 1 diabetes

Pregnant women with type 1 diabetes receiving metformin.

Fifty women in the metformin group completed the study.

Pregnant women with type 1 diabetes receiving placebo.

Fifty women in the placebo group completed the study.

Metformin may reduce prandial insulin needs in pregnant women with type 1 diabetes

Clinician-reference record is usable with limitations in: design, comparator, risk_of_bias.

Patients receiving metformin as monotherapy.

Metformin group (Group M)

Patients receiving metformin 1000 mg once daily were taken in Group M.

Patients receiving metformin plus ranolazine.

Metformin plus ranolazine group (Group M+R)

Patients receiving metformin 1000 mg once daily plus ranolazine were enrolled in Group M+R.

Ranolazine improves glycaemic control when added to metformin in T2DM patients

Participants received 20 mg tofogliflozin per day for 4 weeks.

Tofogliflozin Group

The participants were randomly assigned to a group that received 20 mg tofogliflozin per day for 4 weeks.

Participants received 500 mg metformin per day for 4 weeks.

The participants were randomly assigned to a group that received 500 mg metformin per day for 4 weeks.

Tofogliflozin may improve insulin secretory capacity in some type 2 diabetes patients

Patients received 50 mg of vildagliptin orally twice daily.

Vildagliptin Group

The first group (117 patients) received 50 mg of vildagliptin orally twice daily.

Patients received 500 mg of metformin orally twice daily with meals, with dosage adjustable.

The second group (129 patients) received 500 mg of metformin orally twice daily with meals, and the dosage could be gradually increased by 500 mg per week, up to a maximum daily dose of 2000 mg.

Vildagliptin and Metformin Improve Glycemic Control in Type 2 Diabetes

Structured population data were available for 3 of 3 supporting studies. 1 study described participants with type 2 diabetes. 3 studies described adult participants.

Structured population data were available for 3 of 3 supporting studies. 2 studies described participants with type 2 diabetes. 3 studies described adult participants.

1 supporting study does not have a displayable topic-matched quantitative effect.

Structured population data were available for 4 of 4 supporting studies. 3 studies described participants with type 2 diabetes. 4 studies described adult participants.

Upstream consistency scoring indicates mixed findings across the evidence.

Evidence uses heterogeneous comparison contexts: active_comparator, usual_care.

Structured population data were available for 8 of 8 supporting studies. 4 studies described participants with type 2 diabetes. 8 studies described adult participants.

1 relevant study has unresolved authoritative design evidence and does not contribute to design-specific or RoB-specific claims.

Evidence uses heterogeneous comparison contexts: baseline_within_group, unknown_unresolved, usual_care.

2 supporting studies have high, serious, critical, unclear, or unavailable risk-of-bias information.

Evidence uses heterogeneous comparison contexts: baseline_within_group, usual_care.

2 supporting studies do not have a displayable topic-matched quantitative effect.

Evidence uses heterogeneous comparison contexts: active_comparator, unknown_unresolved.

3 supporting studies have high, serious, critical, unclear, or unavailable risk-of-bias information.

Structured population data were available for 4 of 4 supporting studies. 4 studies described participants with type 2 diabetes. 4 studies described adult participants.

Structured population data were available for 5 of 5 supporting studies. Diabetes type was heterogeneous: 2 studies with type 1 diabetes, 1 studies with type 2 diabetes. Age groups were heterogeneous: 2 studies with adult participants, 1 studies with youth participants.

2 relevant studies have unresolved authoritative design evidence and do not contribute to design-specific or RoB-specific claims.

Evidence uses heterogeneous comparison contexts: baseline_within_group, other, usual_care.

4 of 5 studies with duration data have follow-up of 12 weeks or less.

Structured population data were available for 8 of 8 supporting studies. 7 studies described participants with type 2 diabetes. 7 studies described adult participants.

Evidence uses heterogeneous comparison contexts: active_comparator, baseline_within_group, placebo.

1 supporting study has high, serious, critical, unclear, or unavailable risk-of-bias information.

Structured population data were available for 4 of 4 supporting studies. 4 studies described participants with type 1 diabetes. 2 studies described adult participants.

Structured population data were available for 8 of 8 supporting studies. 6 studies described participants with type 2 diabetes. 7 studies described adult participants.

Evidence uses heterogeneous comparison contexts: active_comparator, unknown_unresolved, usual_care.

Structured population data were available for 8 of 8 supporting studies. Diabetes type was heterogeneous: 4 studies with type 2 diabetes, 1 studies with type 1 diabetes. Age groups were heterogeneous: 4 studies with adult participants, 1 studies with youth participants.

Evidence uses heterogeneous comparison contexts: active_comparator, placebo, usual_care.

5 of 8 studies with duration data have follow-up of 12 weeks or less.

Structured population data were available for 3 of 3 supporting studies. 3 studies described participants with type 2 diabetes. 3 studies described adult participants.

3 of 3 studies with duration data have follow-up of 12 weeks or less.

Evidence uses heterogeneous comparison contexts: active_comparator, placebo.

Evidence uses heterogeneous comparison contexts: active_comparator, baseline_within_group.

Structured population data were available for 3 of 3 supporting studies. Diabetes type was heterogeneous: 1 studies with type 1 diabetes, 1 studies with type 2 diabetes. 2 studies described adult participants.

Structured population data were available for 13 of 13 supporting studies. 11 studies described participants with type 2 diabetes. 12 studies described adult participants.

4 relevant studies have unresolved authoritative design evidence and do not contribute to design-specific or RoB-specific claims.

Evidence uses heterogeneous comparison contexts: active_comparator, baseline_within_group, usual_care.

Evidence uses heterogeneous comparison contexts: unknown_unresolved, usual_care.

Structured population data were available for 3 of 3 supporting studies. Diabetes type was heterogeneous: 2 studies with type 2 diabetes, 1 studies with type 1 diabetes. Age groups were heterogeneous: 2 studies with adult participants, 1 studies with youth participants.

Structured population data were available for 12 of 12 supporting studies. Diabetes type was heterogeneous: 9 studies with type 2 diabetes, 1 studies with type 1 diabetes. 12 studies described adult participants.

9 supporting studies have high, serious, critical, unclear, or unavailable risk-of-bias information.

Structured population data were available for 5 of 5 supporting studies. 5 studies described participants with type 2 diabetes. 4 studies described adult participants.

Structured population data were available for 3 of 3 supporting studies. 2 studies described participants with type 2 diabetes. 2 studies described adult participants.

Structured population data were available for 2 of 3 supporting studies. 2 studies described participants with type 2 diabetes. 2 studies described adult participants.

Evidence uses heterogeneous comparison contexts: active_comparator, placebo, unknown_unresolved.

Structured population data were available for 10 of 10 supporting studies. Diabetes type was heterogeneous: 8 studies with type 2 diabetes, 2 studies with type 1 diabetes. Age groups were heterogeneous: 8 studies with adult participants, 1 studies with youth participants.

Evidence uses heterogeneous comparison contexts: active_comparator, other, usual_care.

3 studies contain conflicting p-value and significance fields; those significance claims are suppressed.

Structured population data were available for 4 of 4 supporting studies. 2 studies described participants with type 2 diabetes. 4 studies described adult participants.

Evidence uses heterogeneous comparison contexts: other, usual_care.

2 of 4 studies with duration data have follow-up of 12 weeks or less.

Structured population data were available for 4 of 4 supporting studies. Diabetes type was heterogeneous: 2 studies with type 2 diabetes, 1 studies with type 1 diabetes. 4 studies described adult participants.

Structured population data were available for 5 of 5 supporting studies. 5 studies described participants with type 2 diabetes. 5 studies described adult participants.

Structured population data were available for 11 of 11 supporting studies. 10 studies described participants with type 2 diabetes. 11 studies described adult participants.

Structured population data were available for 6 of 6 supporting studies. 6 studies described participants with type 2 diabetes. 6 studies described adult participants.

Evidence uses heterogeneous comparison contexts: active_comparator, baseline_within_group, unknown_unresolved, usual_care.

Structured population data were available for 7 of 7 supporting studies. Diabetes type was heterogeneous: 2 studies with type 2 diabetes, 1 studies with type 1 diabetes. 5 studies described adult participants.

Structured population data were available for 5 of 5 supporting studies. 3 studies described participants with type 2 diabetes. 4 studies described adult participants.

Structured population data were available for 5 of 5 supporting studies. Diabetes type was heterogeneous: 4 studies with type 2 diabetes, 1 studies with type 1 diabetes. 3 studies described adult participants.

Evidence uses heterogeneous comparison contexts: baseline_within_group, placebo, usual_care.

Metformin × HbA1c

Available supporting studies