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Research · Medication

Sulfonylureas

Meta-analyses found sulfonylureas lowered HbA1c by about 1.5 points alone and about 0.6 to 1.0 points added to metformin. Large trials found no rise or fall in heart attacks, strokes or deaths against other diabetes drugs. Low blood sugar affected about a third of people over six years, and weight rose about 2 kg.

Add to Bio HackChecked 2026-11-13
Status
Prescription drugs in the US. Glipizide, glimepiride and glyburide are FDA-approved, with diet and exercise, to improve blood sugar control in adults with type 2 diabetes. None is approved for type 1 diabetes, for diabetes in pregnancy or for children. Their labels carry a class warning, not boxed, on a possible increased risk of cardiovascular death.
Also called
glipizide, Glucotrol, Glucotrol XL, glimepiride, Amaryl, glyburide, glibenclamide, Glynase, DiaBeta, Micronase, sulphonylureas, insulin secretagogues
Taken for
type 2 diabetes, blood sugar, HbA1c, low-cost diabetes treatment, add-on to metformin, gestational diabetes, neonatal diabetes

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help3

Reported risks14

What people take it for, and what was found

Shown to help3

Strong

Blood sugar in type 2 diabetes

Shown to lower HbA1c by about 1.5 points more than placebo as single therapy in type 2 diabetes, with no added drop at higher doses.

The numbers and sources
Effect
Across nine trials, sulfonylurea monotherapy lowered HbA1c by 1.51 percentage points more than placebo (95% CI 1.25 to 1.78). Added to other oral treatment it lowered HbA1c by 1.62 points (95% CI 1.0 to 2.24), and added to insulin by 0.46 points (95% CI 0.24 to 0.69). Higher doses did not lower HbA1c more than lower doses [1]. Added to maximal metformin, the drug classes studied lowered HbA1c by a similar 0.64 to 0.97 points against placebo [2]. In a 14-week label trial, glimepiride 1 mg, 4 mg and 8 mg lowered HbA1c by 1.2, 1.8 and 1.8 points against placebo, and in a 22-week trial by 1.1 points [3]. Over 10 years, intensive treatment with a sulfonylurea or insulin held HbA1c at 7.0% against 7.9% on diet [4].
Population
31 trials with a median length of 16 weeks [1]; 11,198 participants in 27 trials of drugs added to metformin [2]; 304 and 249 adults in two glimepiride trials [3]; 3,867 newly diagnosed patients [4].
Sources
[1], [2], [3], [4]
Caveats
Most trials were short. Trial length, drug and duration of diabetes contributed to differences between trials [1].
Limited

Eye, kidney and other small-vessel complications

One trial found 25% fewer small-vessel complications over 10 years with intensive sulfonylurea or insulin treatment than with diet in newly diagnosed type 2 diabetes.

The numbers and sources
Effect
Against diet, intensive treatment with a sulfonylurea or insulin lowered any diabetes-related endpoint by 12% (95% CI 1 to 21) and microvascular endpoints by 25% (95% CI 7 to 40), including the need for retinal laser treatment. Results did not differ between chlorpropamide, glibenclamide and insulin. Diabetes-related death (10% lower, 95% CI -11 to 27) and death from any cause (6% lower, 95% CI -10 to 20) did not differ significantly [4].
Population
3,867 newly diagnosed patients with type 2 diabetes, median age 54, followed over 10 years [4].
Sources
[4]
Caveats
The trial pooled sulfonylureas with insulin in its intensive group, and used chlorpropamide, glibenclamide and glipizide. It did not find fewer large-vessel events [4].
Why limited
This rests on one trial, of 3,867 people. Strength counts independent studies that agree, so one trial is limited at any size.
LimitedVery common

Neonatal diabetes from potassium channel mutations

One study found 90% of patients with diabetes from Kir6.2 mutations stopped insulin on a sulfonylurea, with HbA1c falling from 8.1% to 6.4%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Of 49 patients with diabetes caused by Kir6.2 mutations, 44 (90%) stopped insulin after starting a sulfonylurea. HbA1c improved in everyone who switched, from 8.1% before treatment to 6.4% after 12 weeks, and the improvement was sustained at one year [11].
Population
49 consecutive patients with Kir6.2 (KCNJ11) mutations [11].
Sources
[11]
Caveats
Not an approved use. An uncontrolled study in a rare genetic form of diabetes.

Not shown to help3

Strong

Heart attack, stroke and death

Not shown to lower or raise heart attack, stroke or death against other diabetes drugs, in two large trials and a meta-analysis of 47 trials.

The numbers and sources
Effect
Over a median 6.3 years, the cardiovascular composite occurred in 12.0% on glimepiride and 11.8% on linagliptin (HR 0.98, 95.47% CI 0.84 to 1.14) [5]. Added to metformin, it occurred at 1.5 per 100 person-years on sulfonylureas and 1.5 on pioglitazone (HR 0.96, 95% CI 0.74 to 1.26) [6]. Across 47 trials of at least 52 weeks, sulfonylureas were not associated with death from any cause (OR 1.12, 95% CI 0.96 to 1.30), cardiovascular death (OR 1.12, 95% CI 0.87 to 1.42), heart attack (OR 0.92, 95% CI 0.76 to 1.12) or stroke (OR 1.16, 95% CI 0.81 to 1.66) [7]. A network meta-analysis of 301 trials found no significant differences between drug classes in cardiovascular or all-cause mortality [8].
Population
6,033 adults with type 2 diabetes and raised cardiovascular risk, mean age 64.0 [5]; 3,028 patients on metformin, 11% with a previous cardiovascular event [6]; 37,650 patients in 47 trials [7]; 301 trials [8].
Sources
[5], [6], [7], [8]
Caveats
One trial was stopped early for futility [6]. A Bayesian meta-analysis reached a different result. See the cardiovascular death block under risks.
Moderate

Keeping blood sugar controlled over years

Not shown to hold blood sugar control as long as comparators: 34% failed on glyburide alone by 5 years against 21% on metformin and 15% on rosiglitazone.

The numbers and sources
Effect
As first treatment, the cumulative incidence of monotherapy failure at 5 years was 34% with glyburide, 21% with metformin and 15% with rosiglitazone [9]. Added to metformin, an HbA1c of 7.0% or higher was reached at 30.4 per 100 participant-years on glimepiride, against 26.5 on glargine, 26.1 on liraglutide and 38.1 on sitagliptin [10].
Population
4,360 patients with recently diagnosed type 2 diabetes treated a median 4.0 years [9]; 5,047 participants on metformin followed a mean 5.0 years [10].
Sources
[9], [10]
Caveats
Glimepiride held control longer than sitagliptin in the second trial [10]. Both trials compared active drugs, with no placebo group.
ModerateStudied in pregnancy

Gestational diabetes

Not shown to match insulin in gestational diabetes: glyburide was followed by heavier babies and about twice the newborn low blood sugar.

The numbers and sources
Effect
Against insulin, glibenclamide (glyburide) was associated with higher birth weight (mean difference 109 g, 95% CI 35.9 to 181), more macrosomia (RR 2.62, 95% CI 1.35 to 5.08) and more neonatal hypoglycemia (RR 2.04, 95% CI 1.30 to 3.20). Against glibenclamide, metformin was associated with less maternal weight gain, lower birth weight (209 g lower) and less macrosomia (RR 0.33, 95% CI 0.13 to 0.81). Treatment failure was higher with metformin than with glibenclamide [12].
Population
2,509 women with gestational diabetes needing drug treatment, in 15 articles [12].
Sources
[12]
Caveats
Not an approved use. Short-term outcomes only.

Doses studied

The glimepiride label gives a starting dose of 1 or 2 mg once daily and a maximum of 8 mg once daily. Its placebo-controlled trials used 1, 4 and 8 mg, and its pooled safety data cover 1 to 16 mg a day [3]. The extended-release glipizide label gives a starting dose of 5 mg once daily and a maximum of 20 mg once daily [13]. The glyburide label gives a usual starting dose of 2.5 to 5 mg a day [14].

A meta-analysis of 31 trials found that higher sulfonylurea doses did not lower HbA1c more than lower doses [1].

Risks

Reported risks13

StrongVery common

Low blood sugar

Shown to raise low blood sugar events, affecting 37.7% on glimepiride against 10.6% on linagliptin over six years. Severe episodes occurred in about 2%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Sulfonylureas raised hypoglycemic events against comparators (RR 2.41, 95% CI 1.41 to 4.10) [1]. As monotherapy against metformin the odds were about three times higher (OR 3.13, 95% CI 2.39 to 4.12, risk difference 10%) [8]. Added to metformin, sulfonylureas and glinides had higher rates than placebo (RR range 4.57 to 7.50) [2]. Over a median 6.3 years, at least one episode occurred in 37.7% on glimepiride and 10.6% on linagliptin [5], and over a median 57.3 months in 34% on sulfonylureas and 10% on pioglitazone [6]. In a 22-week label trial, possible hypoglycemia was reported by 19.7% on glimepiride and 3.2% on placebo [3]. On extended-release glipizide, 3.4% had hypoglycemia and none on placebo [13]. Severe hypoglycemia occurred in 2.2% on glimepiride over a mean 5.0 years, against 1.3% on glargine, 1.0% on liraglutide and 0.7% on sitagliptin [10]. Glyburide carried a higher risk than other sulfonylureas (RR 1.83, 95% CI 1.35 to 2.49) [15].
Population
31 trials [1]; 301 trials [8]; 27 trials [2]; 6,033 adults [5]; 3,028 patients [6]; 249 adults in the glimepiride trial [3]; 580 people on extended-release glipizide [13]; 5,047 participants [10]; trials comparing glyburide with other secretagogues [15].
Sources
[1], [8], [2], [5], [6], [3], [13], [10], [15]
Caveats
Definitions of hypoglycemia differed between trials, and some counted symptoms without a glucose reading [3]. The glyburide label names older, debilitated or malnourished people and those with kidney or liver impairment as particularly susceptible [14].
ModerateCommon

Dizziness, nausea and gut upset

Shown to cause dizziness in 5.0% on glimepiride against 2.4% on placebo and nausea in 5.0% against 3.4%, with diarrhea in 5.4% on glipizide against none.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In 11 pooled placebo-controlled trials of glimepiride, dizziness was reported by 5.0% against 2.4% on placebo, nausea by 5.0% against 3.4% and headache by 8.2% against 7.8% [3]. In placebo-controlled trials of extended-release glipizide, dizziness was reported by 6.8% against 5.8%, diarrhea by 5.4% against 0%, tremor by 3.6% against 0% and flatulence by 3.2% against 1.4% [13]. In glyburide trials, gut disturbances such as nausea, fullness and heartburn occurred in 1.8% [14].
Population
745 people on glimepiride and 294 on placebo [3]; 278 on extended-release glipizide and 69 on placebo [13].
Sources
[3], [13], [14]
Caveats
The glipizide placebo group was small, and the glyburide label gives no placebo rate.
ModerateCommon

Liver enzyme rises and liver injury

Shown to raise the liver enzyme ALT above twice the reference limit in 1.9% on glimepiride against 0.8% on placebo. Liver failure appears in postmarketing reports.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In 11 pooled placebo-controlled trials, 1.9% on glimepiride and 0.8% on placebo developed serum ALT above 2 times the upper reference limit. Postmarketing reports include impaired liver function with cholestasis and jaundice, and hepatitis that may progress to liver failure [3]. The glyburide label states that liver enzyme elevations were more frequent when glyburide was taken with bosentan, and lists the combination as contraindicated [14].
Population
745 people on glimepiride and 294 on placebo in 11 trials [3].
Sources
[3], [14]
Caveats
Postmarketing reports have no denominator.
ModerateCommon

Allergic skin reactions

Shown to cause allergic skin reactions such as itching and hives in about 1.5% on glyburide and under 1% on glimepiride in trials.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Allergic skin reactions, including itching, redness, hives and measles-like rashes, occurred in 1.5% of people on glyburide in trials [14], in under 1.5% on extended-release glipizide [13] and in under 1% on glimepiride. Postmarketing reports for glimepiride include anaphylaxis, angioedema and Stevens-Johnson syndrome [3].
Population
Participants in the labels' clinical trials [14][13][3].
Sources
[14], [13], [3]
Caveats
The band above is the glyburide rate. The labels give no placebo rate for skin reactions.
StrongHow often is not known

Weight gain

Shown to raise body weight by about 2 kg against placebo when added to metformin, and by 2.0 to 3.2 kg in a 14-week glimepiride trial.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Added to metformin, sulfonylureas, thiazolidinediones and glinides were associated with weight gain of 1.77 to 2.08 kg against placebo [2]. In a 14-week trial, weight rose against placebo by 2.0 kg on glimepiride 1 mg, 2.8 kg on 4 mg and 3.2 kg on 8 mg [3]. Over 10 years, mean gain was 2.6 kg on chlorpropamide and 1.7 kg on glibenclamide, against 4.0 kg on insulin [4]. Over a median 57.3 months, average gain was under 2 kg on both sulfonylureas and pioglitazone [6].
Population
11,198 participants in 27 trials [2]; 304 adults in the glimepiride trial [3]; 3,867 newly diagnosed patients [4]; 3,028 patients [6].
Sources
[2], [3], [4], [6]
Caveats
Mean changes, with no count of people who gained weight. The placebo group in the label trial lost 2.3 kg after stopping earlier sulfonylurea treatment [3].
LimitedHow often is not known

Low blood sugar after certain antibiotics

Linked to two to four times the odds of low blood sugar when older adults on glipizide or glyburide were prescribed clarithromycin, levofloxacin, sulfamethoxazole-trimethoprim, metronidazole or ciprofloxacin.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Against antimicrobials with no known interaction, hypoglycemia was more frequent after clarithromycin (OR 3.96, 95% CI 2.42 to 6.49), levofloxacin (OR 2.60, 95% CI 2.18 to 3.10), sulfamethoxazole-trimethoprim (OR 2.56, 95% CI 2.12 to 3.10), metronidazole (OR 2.11, 95% CI 1.28 to 3.47) and ciprofloxacin (OR 1.62, 95% CI 1.33 to 1.97). The number needed to harm ranged from 71 for clarithromycin to 334 for ciprofloxacin. These five drugs were associated with 13.2% of all hypoglycemia events in people taking sulfonylureas [17]. The glyburide label describes a possible interaction with ciprofloxacin [14], and the glimepiride label lists clarithromycin, quinolones, sulfonamides, tetracyclines and chloramphenicol among drugs that may raise the glucose-lowering effect [3].
Population
Texas Medicare patients aged 66 or older prescribed glipizide or glyburide, 2006 to 2009 [17].
Sources
[17], [14], [3]
Caveats
Observational. The abstract gives numbers needed to harm, not the share of people with hypoglycemia.
LimitedHow often is not known

Other medicines that raise the chance of low blood sugar

The label lists insulin and other diabetes drugs, ACE inhibitors, NSAIDs, salicylates, coumarins, fluoxetine, MAO inhibitors, fluconazole and oral miconazole as drugs that may deepen low blood sugar.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The glimepiride label lists medicines that may increase the glucose-lowering effect of sulfonylureas: oral antidiabetic drugs, pramlintide, insulin, ACE inhibitors, H2 receptor antagonists, fibrates, somatostatin analogs, anabolic steroids, fluconazole, disopyramide and highly protein-bound drugs such as fluoxetine, nonsteroidal anti-inflammatory drugs, salicylates, sulfonamides, coumarins, probenecid and monoamine oxidase inhibitors. It reports severe hypoglycemia with oral miconazole, and states that fluconazole may raise glimepiride levels [3]. In trials of empagliflozin added to metformin and a sulfonylurea, low glucose readings occurred in 16.1% and 11.5% against 8.4% on placebo [18].
Population
Drug lists in labeling, with no study counts [3]; adults with type 2 diabetes in a 24-week trial [18].
Sources
[3], [18]
Caveats
The label gives no rates for most of these combinations.
LimitedHow often is not known

Medicines that weaken the blood sugar effect

The label lists thiazides and other diuretics, corticosteroids, thyroid hormones, estrogens, oral contraceptives, rifampin and several other drugs as reducing the glucose-lowering effect of sulfonylureas.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The glimepiride label lists medicines that may reduce the glucose-lowering effect: danazol, glucagon, somatropin, protease inhibitors, atypical antipsychotics, barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics and isoniazid. It states that rifampin may lower glimepiride levels, and that colesevelam lowers glimepiride exposure unless glimepiride is taken at least 4 hours earlier [3].
Population
Drug lists in labeling, with no study counts [3].
Sources
[3]
Caveats
The label gives no rates.
LimitedHow often is not known

Beta-blockers and hidden warning signs

The label warns that beta-blockers, clonidine, guanethidine and reserpine may reduce or remove the warning signs of low blood sugar.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The glimepiride label states that the signs of hypoglycemia may be reduced or absent in people taking sympatholytic drugs such as beta-blockers, clonidine, guanethidine and reserpine, and that beta-blockers, clonidine and reserpine may strengthen or weaken the glucose-lowering effect [3].
Population
A statement in labeling, with no study counts [3].
Sources
[3]
Caveats
The label gives no rate.
LimitedHow often is not known

Red blood cell breakdown in G6PD deficiency

The label warns that sulfonylureas can cause hemolytic anemia in people with G6PD deficiency, and reports cases in people without it.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The glimepiride label states that sulfonylureas can cause hemolytic anemia in people with glucose 6-phosphate dehydrogenase deficiency, and that there are postmarketing reports of hemolytic anemia in people on glimepiride without known deficiency [3].
Population
A class warning and postmarketing reports in labeling [3].
Sources
[3]
Caveats
The label gives no rate.
LimitedHow often is not known

Low sodium and low blood counts

The label lists low blood sodium, low white cell and platelet counts and aplastic anemia among reports after marketing. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Postmarketing reports for glimepiride include hyponatremia and the syndrome of inappropriate antidiuretic hormone secretion, most often in people on other medicines or with conditions known to cause low sodium, and leukopenia, agranulocytosis, aplastic anemia, pancytopenia and thrombocytopenia [3].
Population
Voluntary postmarketing reports [3].
Sources
[3]
Caveats
Reports from a population of unknown size.
LimitedHow often is not known

Alcohol

The label states that alcohol may strengthen or weaken the glucose-lowering effect unpredictably, and lists rare flushing reactions with alcohol.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The glimepiride label states that both acute and chronic alcohol intake may potentiate or weaken its glucose-lowering action in an unpredictable fashion, and lists disulfiram-like reactions among postmarketing reports [3]. The glyburide label states that disulfiram-like reactions have been reported very rarely [14].
Population
Statements in labeling, with no study counts [3][14].
Sources
[3], [14]
Caveats
The labels give no rate.
ModerateStudied in pregnancyHow often is not known

Pregnancy and newborn low blood sugar

Linked to about twice the newborn low blood sugar of insulin when glyburide was used in gestational diabetes. Labels report prolonged low blood sugar in exposed newborns.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Against insulin in gestational diabetes, glibenclamide was associated with more neonatal hypoglycemia (RR 2.04, 95% CI 1.30 to 3.20) and macrosomia (RR 2.62, 95% CI 1.35 to 5.08) [12]. The glyburide label reports prolonged severe hypoglycemia lasting 4 to 10 days in newborns whose mothers were taking a sulfonylurea at delivery [14]. The glimepiride label states that published studies and postmarketing experience have not identified drug-associated risks of major birth defects or miscarriage, and that sulfonylureas cross the placenta [3].
Population
2,509 women with gestational diabetes [12]; reports summarized in labeling [14][3].
Sources
[12], [14], [3]
Caveats
The meta-analysis abstract gives risk ratios, not the share of newborns affected.

Mixed results1

ModerateHow often is not known

Cardiovascular death, a class warning on the label

Mixed results: the label warns of cardiovascular death from a 1970s tolbutamide trial, and one meta-analysis found higher mortality, while larger recent trials and another meta-analysis did not.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The labels carry a warning based on the University Group Diabetes Program, in which 823 patients were assigned to four treatments. People treated for 5 to 8 years with diet plus tolbutamide 1.5 g a day had about two and a half times the cardiovascular mortality of people on diet alone, without a significant rise in total mortality [3]. A Bayesian meta-analysis of randomized trial data found higher all-cause mortality (HR 1.26, 95% CI 1.10 to 1.44) and cardiovascular mortality (HR 1.46, 95% CI 1.21 to 1.77) on sulfonylureas than on all other treatments combined [16]. A meta-analysis of 47 trials of second and third generation sulfonylureas found no association with all-cause or cardiovascular mortality (OR 1.12 for each) [7]. In a trial of 6,033 adults, cardiovascular outcomes on glimepiride matched linagliptin (HR 0.98) [5]. Glyburide was not associated with more cardiovascular events than other secretagogues (RR 0.84, 95% CI 0.56 to 1.26) [15].
Population
823 patients in the 1970s trial described on the label [3]; 82 randomized trials and 26 observational studies [16]; 37,650 patients in 47 trials [7]; 6,033 adults [5].
Sources
[3], [16], [7], [5], [15]
Caveats
The label warning rests on tolbutamide, an older drug not covered on this page, and the label itself notes controversy over the trial's interpretation [3]. This is not a boxed warning.

Claims tested and not found

  1. That a higher sulfonylurea dose lowers HbA1c further. Across 31 trials, higher doses did not reduce HbA1c more than lower doses [1].
  2. That modern sulfonylureas raise cardiovascular death. Across 47 trials with 37,650 patients, sulfonylureas were not associated with cardiovascular mortality (OR 1.12, 95% CI 0.87 to 1.42) [7], and over a median 6.3 years glimepiride matched linagliptin on cardiovascular outcomes (HR 0.98) [5].
  3. That sulfonylureas prevent heart attacks and strokes. Intensive sulfonylurea or insulin treatment lowered small-vessel but not large-vessel complications over 10 years [4], and cardiovascular events on sulfonylureas matched pioglitazone (HR 0.96, 95% CI 0.74 to 1.26) [6].
  4. That glyburide matches insulin in gestational diabetes. Across 15 articles, glibenclamide was followed by higher birth weight, more macrosomia and more neonatal hypoglycemia than insulin [12].
  5. That glyburide causes more cardiovascular events or weight gain than other secretagogues. Cardiovascular events (RR 0.84, 95% CI 0.56 to 1.26) and end-of-trial weight (difference 1.69 kg, 95% CI -0.41 to 3.80) did not differ [15].

Sources

  1. Hirst JA, Farmer AJ, Dyar A, Lung TW, Stevens RJ. Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis. Diabetologia. 2013. https://doi.org/10.1007/s00125-013-2856-6
  2. Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010. https://doi.org/10.1001/jama.2010.405
  3. U.S. Food and Drug Administration. Glimepiride tablets, prescribing information (Accord Healthcare). 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b74fbac-9e04-4927-9981-1e3dace89c6d
  4. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). The Lancet. 1998. https://doi.org/10.1016/S0140-6736(98)07019-6
  5. Rosenstock J, Kahn SE, Johansen OE, et al. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA. 2019. https://doi.org/10.1001/jama.2019.13772
  6. Vaccaro O, Masulli M, Nicolucci A, et al. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial. The Lancet Diabetes & Endocrinology. 2017. https://doi.org/10.1016/S2213-8587(17)30317-0
  7. Varvaki Rados D, Catani Pinto L, Reck Remonti L, et al. The Association between Sulfonylurea Use and All-Cause and Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis of Randomized Clinical Trials. PLOS Medicine. 2016. https://doi.org/10.1371/journal.pmed.1001992
  8. Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis. JAMA. 2016. https://doi.org/10.1001/jama.2016.9400
  9. Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. New England Journal of Medicine. 2006. https://doi.org/10.1056/NEJMoa066224
  10. GRADE Study Research Group, Nathan DM, Lachin JM, et al. Glycemia Reduction in Type 2 Diabetes - Glycemic Outcomes. New England Journal of Medicine. 2022. https://doi.org/10.1056/NEJMoa2200433
  11. Pearson ER, Flechtner I, Njølstad PR, et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. New England Journal of Medicine. 2006. https://doi.org/10.1056/NEJMoa061759
  12. Balsells M, García-Patterson A, Solà I, et al. Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis. BMJ. 2015. https://doi.org/10.1136/bmj.h102
  13. U.S. Food and Drug Administration. Glucotrol XL (glipizide) extended release tablets, prescribing information (Roerig, Pfizer). 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eed99b60-d043-4249-9b2a-f05e46fb588d
  14. U.S. Food and Drug Administration. Glyburide tablets USP, prescribing information (Teva Pharmaceuticals USA). 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a56f100f-0f42-4188-81ab-04644b824040
  15. Gangji AS, Cukierman T, Gerstein HC, Goldsmith CH, Clase CM. A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care. 2007. https://doi.org/10.2337/dc06-1789
  16. Bain S, Druyts E, Balijepalli C, et al. Cardiovascular events and all-cause mortality associated with sulphonylureas compared with other antihyperglycaemic drugs: A Bayesian meta-analysis of survival data. Diabetes, Obesity and Metabolism. 2017. https://doi.org/10.1111/dom.12821
  17. Parekh TM, Raji M, Lin YL, et al. Hypoglycemia after antimicrobial drug prescription for older patients using sulfonylureas. JAMA Internal Medicine. 2014. https://doi.org/10.1001/jamainternmed.2014.3293
  18. U.S. Food and Drug Administration. Jardiance (empagliflozin) tablets, prescribing information (Boehringer Ingelheim Pharmaceuticals). 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=faf3dd6a-9cd0-39c2-0d2e-232cb3f67565

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