Sulfonylureas cause more myocardial infarctions, strokes and deaths than metformin (21% higher in 253,690 veterans).
Original statement
السلفونيل يوريا ـ في أتراب 253,690 من قدامى المحاربين بقلم رومي ـ زاد الاحتشاء والسكتة والوفاة 21% مقارنة بالميتفورمين.
verbatim according to source. Translation by the project; the Arabic wording is authoritative.
Translation
Sulfonylureas cause more myocardial infarctions, strokes and deaths than metformin (21% higher in 253,690 veterans).
Origin
- Source status
- Archive editors
- Attribution
- Archive editors (not Elawady)
- Origin
- https://eltayebat.com/rule/oral-diabetes-drugs/
- Attribution uncertainty
- Editorial narrative and study selection written by the archive operators.
- Claimed health effect
Cardiovascular events, death
- Population concerned
Type 2 diabetes
- Geographic restriction by Elawady
none found
Scientific assessment
Potentially true – Some evidence points in favour of the statement, but it is not sufficient for a clear judgement.
Certainty of evidence: low – Further research is likely to change the assessment considerably.
1. What was claimed?
Sulfonylureas raise cardiovascular events and death vs metformin.
2. What is demonstrably correct?
Roumie: 18.2 vs 10.4 events per 1,000 person-years, aHR 1.21 (1.13-1.30) (A-ODD-07); similar observational signals for cancer mortality (A-INS-11) and composite endpoints (A-INS-08). UKPDS 34: metformin was better than sulfonylureas or insulin for any diabetes endpoint and all-cause mortality in overweight patients (I-ODD-01).
3. What is wrong or exaggerated?
'Cause' cannot be concluded from a cohort. In ADVANCE, gliclazide-based intensive control reduced combined events without increasing death (I-INS-01); in UKPDS 33 sulfonylureas did not increase macrovascular disease (A-INS-16) and long-term follow-up showed fewer MIs and deaths (I-INS-02).
4. What remains unclear?
Differences between sulfonylureas (glibenclamide vs gliclazide).
5. Which studies support it?
6. Which studies contradict it?
7. What applies to Germany and Europe?
European (EASD) and German (DDG) guidance follow the same evidence base as the ADA/EASD consensus: individualised HbA1c targets, insulin as mandatory therapy in type 1 diabetes, and SGLT2 inhibitors/GLP-1 receptor agonists for people with cardiovascular or kidney disease. No country-specific difference changes the assessment.
8. What is known about Egypt?
Sulfonylureas are widely used in Egypt because of low cost; their main practical risk is hypoglycaemia, especially with fasting (I-FAST-10).
9. What practical conclusion is appropriate?
Sulfonylureas are second-line drugs with hypoglycaemia risk; RCTs do not show they increase cardiovascular death.
Assessment details
- Rationale for certainty of evidence
Observational cohort with careful adjustment (aHR 1.21) and consistent with Saskatchewan and UK data; but RCTs (UKPDS 33, ADVANCE with gliclazide) did not show cardiovascular harm, and UKPDS showed long-term benefit for sulfonylurea-insulin therapy. Comparative superiority of metformin is plausible (UKPDS 34).
- Source quality
Archive editorial citing a retrospective cohort.
- Regional transferability
US veterans, mostly white men.
- Regional scope of the claim
- general (biological/medical)
- Last reviewed
- 25 October 2026 provisional
In plain language
A large database study found more heart attacks and deaths in people who started sulfonylurea tablets than metformin. Randomised trials did not show such harm, though metformin did somewhat better. The main known problem with sulfonylureas is low blood sugar, especially when people skip meals or fast.
Studies on this claim
Studies supporting the claim (3)
-
Sulfonylurea vs metformin as first drug
Roumie CL et al.. Ann Intern Med 2012 · PMID 23128859 · DOI 10.7326/0003-4819-157-9-201211060-00003Cohort studycited by the Tayebat archivefull text checked★ key studyStarting a sulfonylurea instead of metformin was linked to about 1-4 extra heart events or deaths per 1,000 people per year.
Does the study support the specific claim? Partly · Methodological quality: moderate · Certainty of evidence: see overall assessment of the claim
Original publication · Scientific details
Study explained simply
- What did the researchers want to find out?
Sulfonylurea vs metformin monotherapy on CVD events/death
- How was the study done?
Retrospective cohort (VHA + Medicare) with propensity-matched sensitivity analysis
- How many people, animals or samples were studied?
253,690; Veterans initiating metformin or SU, excluding CKD and serious illness
- What was actually found?
aHR 1.21.
- How large was the observed effect?
aHR 1.21 (1.13-1.30)
- What do the results mean in everyday life?
Metformin is preferred first-line.
- What are the study's limitations?
Observational; mostly white men; under 1 year median follow-up; many stopped treatment; possible residual confounding.
- What does it say about Elawady's specific claim?
Supports C-ODD-11.
- Do the results apply to Germany and Europe?
US veterans.
- What can explicitly not be concluded from this study?
That sulfonylureas cause death.
-
UK database: insulin users vs metformin users
Currie CJ et al.. J Clin Endocrinol Metab 2013 · PMID 23372169 · DOI 10.1210/jc.2012-3042Cohort studycited by the Tayebat archivefull text checked★ key studyPeople treated with insulin alone had about twice the death rate of metformin users, but they were also sicker.
Does the study support the specific claim? Partly · Methodological quality: very low · Certainty of evidence: see overall assessment of the claim
Original publication · Scientific details
Study explained simply
- What did the researchers want to find out?
Risk of adverse events with five glucose-lowering regimens
- How was the study done?
Retrospective cohort, UK General Practice Research Database
- How many people, animals or samples were studied?
84,622 patients; 105,123 exposure periods; Primary care type 2 diabetes
- What was actually found?
Insulin monotherapy associated with higher risks of death, MACE, cancer, complications.
- How large was the observed effect?
aHR 2.197 death
- What do the results mean in everyday life?
Shows insulin users fare worse, not that insulin causes it.
- What are the study's limitations?
Insulin users had longer diabetes (5.2 vs 1.5 years), more kidney and heart disease; ~3 years follow-up; censoring at treatment switch; authors note confounding by indication; authors have industry ties.
- What does it say about Elawady's specific claim?
Main observational support for C-INS-05.
- Do the results apply to Germany and Europe?
UK data.
- What can explicitly not be concluded from this study?
That insulin causes death, cancer or kidney failure; any insulin dose-response.
-
Metformin in overweight type 2 diabetes (UKPDS 34)
UKPDS Group. Lancet 1998 · PMID 9742977Randomised controlled trialindependent cross-checkabstract only checked★ key studyMetformin reduced deaths from any cause by about a third over 10 years.
Does the study support the specific claim? No · Methodological quality: moderate · Certainty of evidence: see overall assessment of the claim
Original publication · Scientific details
Study explained simply
- What did the researchers want to find out?
Intensive control with metformin in overweight type 2 diabetes
- How was the study done?
RCT within UKPDS (UKPDS 34)
- How many people, animals or samples were studied?
753 (main comparison); Overweight newly diagnosed type 2 diabetes, mean age 53
- What was actually found?
Mortality -36%.
- How large was the observed effect?
RR reduction 36% (9-55)
- What do the results mean in everyday life?
Metformin is protective.
- What are the study's limitations?
Small arms; Open-label; Conflicting supplementary result
- What does it say about Elawady's specific claim?
- Do the results apply to Germany and Europe?
UK.
- What can explicitly not be concluded from this study?
Effects in non-overweight patients.
No study in this group is marked as key.
Studies contradicting or limiting the claim (3)
-
ADVANCE: intensive control to HbA1c 6.5%
ADVANCE Collaborative Group; Patel A et al.. N Engl J Med 2008 · PMID 18539916 · DOI 10.1056/NEJMoa0802987Randomised controlled trialindependent cross-checkfull text checked★ key studyFewer kidney complications and no extra deaths, but more severe hypoglycaemia.
Does the study support the specific claim? No · Methodological quality: high · Certainty of evidence: see overall assessment of the claim
Original publication · Scientific details
Study explained simply
- What did the researchers want to find out?
Effect of intensive glucose control (gliclazide MR-based, HbA1c <=6.5%) on vascular outcomes
- How was the study done?
Multicentre factorial RCT (ADVANCE glucose arm)
- How many people, animals or samples were studied?
11,140; Type 2 diabetes with high vascular risk
- What was actually found?
10% fewer combined events; no mortality difference.
- How large was the observed effect?
HR 0.90 (0.82-0.98)
- What do the results mean in everyday life?
Moderately intensive control is safe and protects kidneys.
- What are the study's limitations?
Open-label; kidney benefit mainly less protein in urine; underpowered for heart attacks/strokes; funded by the drug's manufacturer (analysis independent).
- What does it say about Elawady's specific claim?
Limits C-INS-04 (intensive control is not uniformly harmful); contradicts C-ODD-11.
- Do the results apply to Germany and Europe?
Multinational trial including European sites or directly applicable to EU practice.
- What can explicitly not be concluded from this study?
Benefit for heart attacks/stroke.
-
UKPDS: tablets or insulin for new type 2 diabetes
UKPDS Group. Lancet 1998 · PMID 9742976Randomised controlled trialcited by the Tayebat archiveabstract only checked★ key studyBetter sugar control with tablets or insulin cut eye/kidney complications by a quarter; insulin caused more weight gain and low-sugar episodes.
Does the study support the specific claim? Partly · Methodological quality: high · Certainty of evidence: see overall assessment of the claim
Original publication · Scientific details
Study explained simply
- What did the researchers want to find out?
Intensive control with sulfonylurea or insulin vs diet on complications
- How was the study done?
Multicentre RCT (UKPDS 33)
- How many people, animals or samples were studied?
3,867; Newly diagnosed type 2 diabetes, median age 54
- What was actually found?
Microvascular -25%; more hypoglycaemia and weight gain with insulin.
- How large was the observed effect?
RR reduction 25% microvascular
- What do the results mean in everyday life?
Insulin helps prevent complications but has side effects.
- What are the study's limitations?
Open-label; Older drug regimens
- What does it say about Elawady's specific claim?
Supports weight/hypoglycaemia (C-INS-01); contradicts C-INS-03, C-INS-05, C-DIAB-01.
- Do the results apply to Germany and Europe?
UK; directly relevant.
- What can explicitly not be concluded from this study?
That insulin is harmful overall.
-
UKPDS legacy: 10 years after the trial
Holman RR et al.. N Engl J Med 2008 · PMID 18784090 · DOI 10.1056/NEJMoa0806470Randomised controlled trialindependent cross-checkabstract only checked★ key studyPeople treated intensively early with sulfonylureas or insulin had 15% fewer heart attacks and 13% fewer deaths years later.
Does the study support the specific claim? No · Methodological quality: high · Certainty of evidence: see overall assessment of the claim
Original publication · Scientific details
Study explained simply
- What did the researchers want to find out?
Do UKPDS benefits persist and do macrovascular effects emerge?
- How was the study done?
Post-trial monitoring of an RCT (UKPDS 80)
- How many people, animals or samples were studied?
4,209 randomised; 3,277 monitored; Newly diagnosed type 2 diabetes from UKPDS
- What was actually found?
Legacy reductions in MI and death.
- How large was the observed effect?
Death -13% (SU/insulin), -27% (metformin)
- What do the results mean in everyday life?
Early good control pays off for decades.
- What are the study's limitations?
Post-trial therapy not controlled; Questionnaire follow-up
- What does it say about Elawady's specific claim?
Contradicts C-INS-03, C-INS-05 and C-DIAB-01: early insulin/SU therapy reduced MI and death long-term.
- Do the results apply to Germany and Europe?
UK; directly relevant.
- What can explicitly not be concluded from this study?
Effects of extreme targets in late disease.
No study in this group is marked as key.
Studies with mixed or unclear results (0)
No studies in this group.
Regional context
Germany / EU
European (EASD) and German (DDG) guidance follow the same evidence base as the ADA/EASD consensus: individualised HbA1c targets, insulin as mandatory therapy in type 1 diabetes, and SGLT2 inhibitors/GLP-1 receptor agonists for people with cardiovascular or kidney disease. No country-specific difference changes the assessment.
Egypt
Sulfonylureas are widely used in Egypt because of low cost; their main practical risk is hypoglycaemia, especially with fasting (I-FAST-10).
What applies in my country?
General scientific assessment
Potentially true An observational signal, not confirmed by trials; hypoglycaemia is the established risk.
This statement concerns biological or medical relationships. The scientific assessment above applies regardless of the country; country-specific food data do not change it.
References
- Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study.. Roumie CL et al.. Ann Intern Med 2012 · PMID 23128859 · DOI 10.7326/0003-4819-157-9-201211060-00003
- Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes.. Currie CJ et al.. J Clin Endocrinol Metab 2013 · PMID 23372169 · DOI 10.1210/jc.2012-3042
- Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group.. UKPDS Group. Lancet 1998 · PMID 9742977
- Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.. ADVANCE Collaborative Group; Patel A et al.. N Engl J Med 2008 · PMID 18539916 · DOI 10.1056/NEJMoa0802987
- Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.. UKPDS Group. Lancet 1998 · PMID 9742976
- 10-year follow-up of intensive glucose control in type 2 diabetes.. Holman RR et al.. N Engl J Med 2008 · PMID 18784090 · DOI 10.1056/NEJMoa0806470