Table 1

Characteristics of the included studies

Author (year)Study designComparisonRegionSample size (men/women)AgeAssessment methodEstimate effect (95% CI)NOS scoresAdjustment factors
Lee et al 201128 CohortMetformin vs non-metforminAsiaExp: 11 212 (–)
Con: 4193 (–)
≥20ICDHR: 0.44 (0.07 to 2.61)7Adjusted*
Ruiter et al 201111 CohortMetformin vs sulfonylureaEuropeExp: 52 698
(24 432/28 266)
Con: 32 591
(15 699/16 892)
≥18ICD-9HR: 0.90 (0.82 to 0.97)6Adjusted†
Tseng 201712 CohortMetformin vs non-MetforminAsiaExp: 288 013
(155 140/132 873)
Con: 16 216
(9293/6923)
Exp: 56.62±10.24
Con: 59.14±10.39
ICD-9-CMHR: 0.56 (0.33 to 0.94)8Adjusted‡
Murff et al 201829 CohortMetformin vs sulfonylureaNorth AmericaExp: 88 581
(84 267/4314)
Con: 49 282
(48 056/1226)
Exp: 62 (56–71)
Con: 67 (58–76)
ICD-9-CMHR: 0.85 (0.65 to 1.11)7Adjusted§
Oh and Song 201913 CohortMetformin vs non-metforminAsiaExp: 29 974 (–)
Con: 36 653 (–)
≥18ICD-10HR: 0.38 (0.13 to 1.13)8Adjusted¶
Wang et al 201917 CohortMetformin vs non-metforminEuropeExp: 411 603
(239 360/172 243)
Con: 4 116 030
(2 393 600/1 722 430)
Exp:59.0 (±13.7) Con:59.0 (±13.7)ICD-10 and ICD-0–3HR: 0.68 (0.54 to 0.85)8Adjusted**
Sung et al 202015 CohortMetformin vs non-metformin/asprinAsiaExp: 11 365 (5285/6080)
Con: 277 932 (148 276/129 656)
≥18ICD-9/10HR: 0.27 (0.12 to 0.59)8Adjusted††
  • *Adjusted for age, gender, other oral anti-hyperglycemic medication, Charlson comorbidity index score and duration of metformin exposure.

  • †Adjusted for age at first OGLD prescription, sex, year in which the first OGLD prescription was dispensed, number of unique drugs used in the year and number of hospitalisations in the year before the start of the OGLD.

  • ‡Adjusted for age, sex, occupation, living region, hypertension, dyslipidaemia, obesity, nephropathy, eye disease, stroke, ischaemic heart disease, peripheral arterial disease, chronic obstructive pulmonary disease, tobacco abuse, alcohol-related diagnoses, HP infection, EBV-related diagnoses, HBV infection, HCV infection, ACEI/ARB, calcium channel blocker, statin, fibrate, aspirin, NSAID.

  • §Adjusted for age, sex, race, date of cohort entry, body mass index, blood pressure, glomerular filtration rate, haemoglobin A1c, low-density lipoprotein levels, smoking status, select medications, comorbid illnesses number of medications and number of outpatient visits.

  • ¶Adjusted for age, sex, income level, residence, hypertension, coronary artery disease, cerebrovascular disease, psychobehavioral disorder, musculoskeletal disorders, chronic kidney disease, dyslipidaemia, anaemia, chronic obstructive pulmonary disease, arrhythmia, liver cirrhosis, surgery in 2010, hospital visit days in 2010, other antidiabetic medications use.

  • **Adjusted for age, sex, calendar year, residence, smoking, and alcohol overconsumption, nonsteroidal anti-inflammatory drugs/aspirin and statin use.

  • ††Adjusted for age, sex, comorbidities and other medications.

  • ACEI/ARB, Angiotensin-converting enzyme inhibitor/Angiotensin receptor blocker; Con, Control group; EBV, Epstein-Barr virus; Exp, Experimental group; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HP, Helicobacter pylori; ICD, Classification of Diseases; NOS, Newcastle-Ottawa Scale; NSAID, non-steroidal anti-inflammatory drugs; OGLD, Oral glucose-lowering drug.