What does the research show about insulin?

Insulin

Intensive insulin treatment in type 1 diabetes cut eye, kidney and nerve complications by about 40% to 76% in trials. In type 2 diabetes insulin lowered HbA1c, without fewer heart attacks or deaths. Long-acting analogs matched NPH on HbA1c with somewhat fewer lows. Severe low blood sugar and weight gain were the main harms.

Add to Bio HackChecked 2026-11-13

Status: Prescription drugs in the US. Insulin glargine, insulin lispro and insulin aspart are FDA-approved to improve blood sugar control in adults and children with diabetes mellitus. Insulin degludec is approved for the same use from age 1. No insulin is approved to prevent diabetes or for people without diabetes.
Also called: insulin glargine, Lantus, Basaglar, Toujeo, Semglee, insulin lispro, Humalog, Admelog, insulin aspart, NovoLog, Fiasp, insulin degludec, Tresiba, NPH insulin, Humulin N, Novolin N, regular human insulin, basal insulin, mealtime insulin, long-acting insulin, rapid-acting insulin
Taken for: type 1 diabetes, type 2 diabetes, blood sugar, HbA1c, preventing diabetes complications, eye and kidney protection in diabetes, diabetes in pregnancy

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 help6

ModerateShown to cut new eye disease by about 76%, kidney protein leakage by 39% to 54% and nerve damage by 60% with intensive insulin treatment in type 1 diabetes.
ModerateShown to lower HbA1c in type 2 diabetes, to 7.0% against 7.9% on diet over 10 years in one trial, with 25% fewer small-vessel complications.
ModerateShown to give HbA1c similar to NPH insulin with fewer people having low blood sugar, while differences in severe episodes were small.
ModerateShown to give the same HbA1c as glargine with fewer low blood sugar episodes, including severe episodes in 4.9% against 6.6% in one large trial.
LimitedOne trial found 42% fewer cardiovascular events over a mean 17 years in people with type 1 diabetes first assigned to intensive insulin treatment.
LimitedOne trial found new diabetes in 30% on insulin glargine against 35% on standard care, measured about 3 months after treatment stopped.

Reported risks14

StrongShown to cause severe low blood sugar in about 6% to 17% of adults with type 1 diabetes within 28 weeks, two to three times more often under intensive treatment.Very common
ModerateLinked to thickened fatty lumps at injection sites in about 38% of insulin users across 26 studies, with wide variation between studies.Very common
LimitedSmall trials found retinopathy worsened in 34.7% after one year of intensive control against 14.9% on conventional control, before the long-term benefit appeared.Very common
StrongShown to raise severe low blood sugar in type 2 diabetes, to 5.6% on insulin glargine against 1.8% on standard care over 6.2 years in one trial.Common
ModerateShown to raise body weight, by a mean 4.0 kg over 10 years in one type 2 diabetes trial and 1.6 kg over 6 years in another.How often is not known
LimitedCase reports: coma from severe low blood sugar has been described in a bodybuilder injecting insulin without diabetes. No rate is known.How often is not known
LimitedThe label warns that all insulins shift potassium into cells and can cause low blood potassium. It gives no rate.How often is not known
LimitedThe label warns that thiazolidinedione diabetes drugs taken with insulin can cause dose-related fluid retention, which may lead to or worsen heart failure.How often is not known
LimitedThe label lists other diabetes drugs, ACE inhibitors, angiotensin receptor blockers, fluoxetine, MAO inhibitors, salicylates and sulfonamide antibiotics as drugs that may raise the risk of low blood sugar.How often is not known
LimitedThe label lists corticosteroids, diuretics, estrogens, oral contraceptives, thyroid hormones, atypical antipsychotics and several other drugs as lowering the blood sugar effect of insulin.How often is not known
LimitedThe label warns that beta-blockers, clonidine, guanethidine and reserpine may reduce or remove the warning signs of low blood sugar.How often is not known
LimitedThe label reports severe, life-threatening generalized allergy including anaphylaxis with insulin, and redness, itching and swelling at injection sites. It gives no rate.How often is not known
LimitedThe label warns that pump or infusion set failure can rapidly lead to high blood sugar and ketoacidosis. Trials found more ketoacidosis only where pumps were used.How often is not known
LimitedThe label reports medication errors after marketing in which rapid-acting and other insulins were given by accident in place of glargine.How often is not known

What people take it for, and what was found

Shown to help6

Moderate

Eye, kidney and nerve complications in type 1 diabetes

Shown to cut new eye disease by about 76%, kidney protein leakage by 39% to 54% and nerve damage by 60% with intensive insulin treatment in type 1 diabetes.

The numbers and sources

Effect: In people with type 1 diabetes and no eye disease, intensive insulin treatment lowered the risk of developing retinopathy by 76% (95% CI 62 to 85) against conventional treatment. In people with mild retinopathy it slowed progression by 54% (95% CI 39 to 66). Across both groups it lowered microalbuminuria by 39% (95% CI 21 to 52), albuminuria by 54% (95% CI 19 to 74) and clinical neuropathy by 60% (95% CI 38 to 74) [1]. A Cochrane review of 12 trials found retinopathy developed in 6.2% on intensive control against 23.2% on conventional control (RR 0.27, 95% CI 0.18 to 0.42), nephropathy in 16.3% against 28.4% (RR 0.56, 95% CI 0.46 to 0.68) and neuropathy in 4.9% against 13.9% (RR 0.35, 95% CI 0.23 to 0.53) [2].
Population: 1,441 people with type 1 diabetes, assigned to an insulin pump or three or more daily injections, or to one or two daily injections [1]; 2,230 patients in 12 trials followed for 1 to 6.5 years [2].
Sources: [1], [2]
Caveats: The trials compared more intensive with less intensive insulin treatment. Neither arm went without insulin. The largest trial dominates the review [2]. Once complications were present, the effect was weaker for eye disease and uncertain for kidney disease [2].

Moderate

Blood sugar and complications in type 2 diabetes

Shown to lower HbA1c in type 2 diabetes, to 7.0% against 7.9% on diet over 10 years in one trial, with 25% fewer small-vessel complications.

The numbers and sources

Effect: In newly diagnosed type 2 diabetes, intensive treatment with insulin or a sulfonylurea held HbA1c at 7.0% against 7.9% on diet over 10 years, with no difference between agents. The risk of any diabetes-related endpoint was 12% lower (95% CI 1 to 21) and of microvascular endpoints 25% lower (95% CI 7 to 40) [3]. Added to metformin, glargine kept HbA1c below 7.0% for longer than glimepiride or sitagliptin. An HbA1c of 7.0% or higher was reached at 26.5 per 100 participant-years on glargine, 26.1 on liraglutide, 30.4 on glimepiride and 38.1 on sitagliptin [4]. In a 52-week label trial of glargine added to oral drugs, HbA1c fell by 0.5 points from a baseline of 9.0% [5]. In a network meta-analysis, drug classes added to metformin were associated with similar HbA1c levels [6].
Population: 3,867 newly diagnosed patients, median age 54 [3]; 5,047 participants on metformin followed a mean of 5.0 years [4]; 570 adults in the label trial [5]; 301 trials of glucose-lowering drugs [6].
Sources: [3], [4], [5], [6]
Caveats: The 10-year trial pooled insulin with sulfonylureas in its intensive group, and found no drop in diabetes-related death or death from any cause [3]. A meta-analysis of 20 trials found no effect of insulin on any clinical outcome in type 2 diabetes [7].

Moderate

Long-acting analogs compared with NPH insulin

Shown to give HbA1c similar to NPH insulin with fewer people having low blood sugar, while differences in severe episodes were small.

The numbers and sources

Effect: In type 2 diabetes, changes in HbA1c were comparable between long-acting analogs and NPH insulin, and glargine and detemir each lowered confirmed and nighttime hypoglycemia. For severe hypoglycemia the risk ratio was 0.68 for glargine (95% CI 0.46 to 1.01, absolute reduction 1.2%) and 0.45 for detemir (95% CI 0.17 to 1.20) [10]. In type 1 diabetes, severe hypoglycemia occurred in 8.5% on detemir against 11.5% on NPH (RR 0.69, 95% CI 0.52 to 0.92) and in 10.2% on glargine against 12.5% on NPH (RR 0.84, 95% CI 0.67 to 1.04). HbA1c did not differ between detemir and NPH (mean difference 0.01%, 95% CI -0.1 to 0.1) [11]. In label trials in type 2 diabetes, the HbA1c difference between glargine and NPH ranged from 0.1 points lower to 0.2 points higher [5].
Population: 24 trials in type 2 diabetes lasting 24 weeks to 5 years [10]; 8,784 participants with type 1 diabetes in 26 trials, 21% of them children [11]; 2,105 adults in three label trials [5].
Sources: [10], [11], [5]
Caveats: All of the type 2 trials had unclear or high risk of bias, and certainty for severe hypoglycemia was low or very low [10]. No trial compared degludec with NPH insulin [10][11].

Moderate

Degludec compared with glargine

Shown to give the same HbA1c as glargine with fewer low blood sugar episodes, including severe episodes in 4.9% against 6.6% in one large trial.

The numbers and sources

Effect: In type 2 diabetes at high cardiovascular risk, HbA1c at 24 months was 7.5% in both groups. Severe hypoglycemia occurred in 4.9% on degludec against 6.6% on glargine (rate ratio 0.60) [9]. In type 1 diabetes, symptomatic hypoglycemia during the maintenance period was lower on degludec (rate ratio 0.89, 95% CI 0.85 to 0.94), and severe hypoglycemia occurred in 10.3% against 17.1% [12]. In insulin-treated type 2 diabetes, 22.5% on degludec against 31.6% on glargine had a symptomatic episode, while severe hypoglycemia did not differ (1.6% against 2.4%) [13]. A Cochrane review of four trials in type 1 diabetes found no evidence of a clinically relevant difference between degludec and glargine on its main outcomes [11].
Population: 7,637 patients with type 2 diabetes [9]; 501 patients with type 1 diabetes and a risk factor for hypoglycemia [12]; 721 patients with type 2 diabetes and a risk factor for hypoglycemia [13]; four trials in type 1 diabetes [11].
Sources: [9], [12], [13], [11]
Caveats: The three trials were funded by the maker of degludec, and two enrolled only people at raised risk of hypoglycemia [12][13]. The Cochrane review did not find a relevant difference [11].

Limited

Heart disease in type 1 diabetes

One trial found 42% fewer cardiovascular events over a mean 17 years in people with type 1 diabetes first assigned to intensive insulin treatment.

The numbers and sources

Effect: Over a mean 17 years of follow-up, 46 cardiovascular events occurred in 31 patients first assigned to intensive treatment against 98 events in 52 patients assigned to conventional treatment. Intensive treatment lowered the risk of any cardiovascular event by 42% (95% CI 9 to 63) and of nonfatal heart attack, stroke or cardiovascular death by 57% (95% CI 12 to 79) [16].
Population: 1,441 patients with type 1 diabetes treated for a mean 6.5 years, 93% of them then followed observationally [16].
Sources: [16]
Caveats: Events were few. After the randomized phase ended, follow-up was observational. A Cochrane review found too few heart attacks and strokes across trials to draw a conclusion [2].
Why limited: This rests on one trial, of 1,441 people. Strength counts independent studies that agree, so one trial is limited at any size.

Limited

Delaying type 2 diabetes in people with raised blood sugar

One trial found new diabetes in 30% on insulin glargine against 35% on standard care, measured about 3 months after treatment stopped.

The numbers and sources

Effect: Among 1,456 participants without diabetes at the start, new diabetes was diagnosed about 3 months after therapy was stopped in 30% on glargine against 35% on standard care (OR 0.80, 95% CI 0.64 to 1.00) [8].
Population: 1,456 people with impaired fasting glucose or impaired glucose tolerance within a trial of 12,537, followed a median 6.2 years [8].
Sources: [8]
Caveats: Not an approved use. The upper confidence limit reached 1.00. In the same trial, glargine raised severe hypoglycemia and weight [8].

Mixed results1

Moderate

Rapid-acting analogs compared with regular human insulin

Mixed results: rapid-acting analogs lowered HbA1c 0.15 points more than regular human insulin in type 1 diabetes, with no clear difference in type 2 diabetes.

The numbers and sources

Effect: In adults with type 1 diabetes, HbA1c was 0.15 points lower on rapid-acting analogs (95% CI 0.1 to 0.2), and severe hypoglycemia did not differ (OR 0.89, 95% CI 0.71 to 1.12) [14]. In adults with type 2 diabetes, HbA1c change did not differ (mean difference -0.03%, 95% CI -0.16 to 0.09), and no trial showed a clear difference in severe hypoglycemia [15].
Population: 2,693 participants with type 1 diabetes in 9 trials of 24 to 52 weeks [14]; 2,751 participants with type 2 diabetes in 10 trials of 24 to 104 weeks [15].
Sources: [14], [15]
Caveats: None of the trials was blinded, and the evidence was rated low or very low quality. No trial measured long-term complications or mortality as a main outcome [14][15].

Not shown to help1

Strong

Heart attack, stroke and death in type 2 diabetes

Not shown to lower heart attack, stroke, cardiovascular death or death from any cause in type 2 diabetes, in one large trial and two meta-analyses.

The numbers and sources

Effect: Over a median 6.2 years, cardiovascular outcomes occurred at 2.94 per 100 person-years on insulin glargine and 2.85 on standard care (HR 1.02, 95% CI 0.94 to 1.11) [8]. Across 20 trials, insulin did not change death from any cause against other glucose-lowering drugs (RR 0.99, 95% CI 0.92 to 1.06) or against diet or placebo (RR 0.92, 95% CI 0.80 to 1.07), and did not change cardiovascular death (RR 0.99, 95% CI 0.90 to 1.09) [7]. A network meta-analysis of 301 trials found no significant differences between any drug class in cardiovascular or all-cause mortality [6]. Between two basal insulins, major cardiovascular events occurred in 8.5% on degludec and 9.3% on glargine (HR 0.91, 95% CI 0.78 to 1.06) [9].
Population: 12,537 people with cardiovascular risk factors and impaired fasting glucose, impaired glucose tolerance or type 2 diabetes, mean age 63.5 [8]; 18,599 patients in 20 trials [7]; 301 trials [6]; 7,637 patients with type 2 diabetes [9].
Sources: [8], [7], [6], [9]
Caveats: The glargine trial was funded by the manufacturer and targeted a normal fasting glucose [8].

Claimed, not studied in people1

Untested

Muscle gain in people without diabetes

Not studied in people. Bodybuilders report injecting insulin to build muscle, and a review found little evidence-based human data for the practice.

No study in people. This rests on what users report, how it acts in the body.

The numbers and sources

Effect: A review of hormones used for anabolic purposes describes insulin as commonly abused by professional and recreational athletes, and states that the belief in added muscle mass is widespread among users despite a paucity of evidence-based data in humans [17]. In a questionnaire study of 92 male recreational bodybuilders, 43% reported regular hormone use, and 38% of those reported using insulin [18].
Population: 92 male recreational bodybuilders answering anonymous questionnaires [18]. No controlled trial in people without diabetes was located [17].
Sources: [17], [18]
Caveats: Not an approved use. What users report is not a measured effect. See the risk block on low blood sugar in people without diabetes.

Doses studied

Insulin doses in trials were adjusted to each person's glucose readings. The glargine label gives a starting dose of 0.2 units/kg or up to 10 units once daily for people with type 2 diabetes new to insulin. In its 52-week trial with oral drugs, the mean basal dose rose from 14 units by 12 units, and in its 5-year trial from 39 units by 23 units [5]. The large glargine outcome trial adjusted the dose to a fasting glucose of 95 mg/dL or below [8].

The type 1 diabetes complications trial compared an insulin pump or three or more daily injections, guided by frequent glucose monitoring, with one or two daily injections [1]. A pharmacology study on the insulin aspart label used 0.15 units/kg [19].

Risks

Reported risks14

StrongVery common

Severe low blood sugar in type 1 diabetes

Shown to cause severe low blood sugar in about 6% to 17% of adults with type 1 diabetes within 28 weeks, two to three times more often under intensive treatment.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Intensive insulin treatment raised severe hypoglycemia two to threefold against conventional treatment [1]. A Cochrane review also found a higher risk under intensive control, clearest in the largest trial [2]. In adult label trials of glargine, severe symptomatic hypoglycemia occurred in 6.5% to 10.6% on glargine and 5.2% to 15.0% on NPH insulin over 16 to 28 weeks, and in children in 23.0% against 28.6% over 26 weeks [5]. On insulin aspart by injection it occurred in 17% of adults and 6% of children at 24 weeks [19]. Pooled across trials, 10.2% on glargine and 12.5% on NPH had a severe episode [11].
Population: 1,441 people in the complications trial [1]; 12 trials [2]; 1,738 adults and 349 children in four label trials [5]; 2,350 participants in 9 trials [11].
Sources: [1], [2], [5], [19], [11]
Caveats: There is no placebo group in type 1 diabetes, so rates are compared between insulins or treatment intensities. Rates depend on how severe hypoglycemia was defined [19].

ModerateVery common

Thickened or pitted skin at injection sites

Linked to thickened fatty lumps at injection sites in about 38% of insulin users across 26 studies, with wide variation between studies.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Across 26 studies, the pooled prevalence of lipohypertrophy was 38% (95% CI 29 to 46), 34% in type 1 diabetes and 49% in type 2 diabetes [21]. The label reports lipoatrophy, lipohypertrophy and localized cutaneous amyloidosis at injection sites. It states that injecting into affected areas has been reported to cause high blood sugar, and a sudden change to an unaffected site low blood sugar. Injection site pain was reported by 2.7% on glargine against 0.7% on NPH insulin [5].
Population: 12,493 insulin-treated participants in 26 studies [21]; adults in glargine trials [5].
Sources: [21], [5]
Caveats: Prevalence studies, with very high heterogeneity (I² 99.1%) [21].

LimitedVery common

Early worsening of eye disease when control tightens quickly

Small trials found retinopathy worsened in 34.7% after one year of intensive control against 14.9% on conventional control, before the long-term benefit appeared.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: In two trials, retinopathy had progressed after one year in 17 of 49 people on intensive glucose control (34.7%) against 7 of 47 on conventional control (14.9%) (RR 2.32, 95% CI 1.16 to 4.63). In trials lasting at least two years, intensive control lowered progression (23.2% against 38.7%) [2]. The labels state that rapid improvement in glucose control has been associated with a temporary change in vision, worsening of diabetic retinopathy and acute painful nerve symptoms [5][19].
Population: 96 participants with type 1 diabetes in two trials [2].
Sources: [2], [5], [19]
Caveats: Rated low quality evidence. The band above comes from 96 people who mostly had eye disease at the start [2].

StrongCommon

Severe low blood sugar in type 2 diabetes

Shown to raise severe low blood sugar in type 2 diabetes, to 5.6% on insulin glargine against 1.8% on standard care over 6.2 years in one trial.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Severe hypoglycemia was more frequent with insulin than with other glucose-lowering drugs across 20 trials (RR 1.70, 95% CI 1.51 to 1.91) [7]. In a network meta-analysis, basal insulin alone carried the highest odds of hypoglycemia against metformin (OR 17.9, 95% CI 1.97 to 162, risk difference 10%) [6]. Over a median 6.2 years, 5.6% on glargine and 1.8% on standard care had severe symptomatic hypoglycemia [5], at 1.00 against 0.31 per 100 person-years [8]. In label trials of 28 weeks to 5 years, it occurred in 0.4% to 7.8% on glargine and 1.1% to 11.9% on NPH [5]. Major episodes occurred in 1.8% a year on insulin against 0.7% on diet [3]. Added to metformin, severe hypoglycemia occurred in 1.3% on glargine, 2.2% on glimepiride, 1.0% on liraglutide and 0.7% on sitagliptin over a mean 5.0 years [4].
Population: 18,599 patients in 20 trials [7]; 301 trials [6]; 12,504 people in the outcome trial [5][8]; 3,867 newly diagnosed patients [3]; 5,047 participants on metformin [4].
Sources: [7], [6], [5], [8], [3], [4]
Caveats: The confidence interval in the network meta-analysis was very wide [6]. Rates were lower in people recently diagnosed and on metformin [4].

LimitedHow often is not known

Low blood sugar in people without diabetes who inject insulin

Case reports: coma from severe low blood sugar has been described in a bodybuilder injecting insulin without diabetes. No rate is known.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: A case report describes a 30-year-old male bodybuilder who presented in a coma from severe hypoglycemia needing repeated glucose infusions, later traced to concealed insulin injections [20]. A review of anabolic hormone use lists the side effects of insulin used this way and notes that users are reluctant to volunteer information [17].
Population: One case report [20] and a narrative review [17].
Sources: [20], [17]
Caveats: Case reports have no denominator.

ModerateHow often is not known

Weight gain

Shown to raise body weight, by a mean 4.0 kg over 10 years in one type 2 diabetes trial and 1.6 kg over 6 years in another.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In newly diagnosed type 2 diabetes, people assigned insulin gained a mean 4.0 kg, against 2.6 kg on chlorpropamide and 1.7 kg on glibenclamide [3]. Over a median 6.2 years, median weight rose by 1.6 kg on glargine and fell by 0.5 kg on standard care [8]. Several trials in type 1 diabetes found greater weight gain under intensive control [2]. There was no clear difference in weight gain between long-acting analogs and NPH insulin [10]. The label attributes the gain to the anabolic effects of insulin and less glucose lost in urine [5].
Population: 3,867 newly diagnosed patients [3]; 12,537 people with raised cardiovascular risk [8]; 12 trials in type 1 diabetes [2]; 24 trials in type 2 diabetes [10].
Sources: [3], [8], [2], [10], [5]
Caveats: Mean changes, with no count of people who gained weight.

LimitedHow often is not known

Low potassium

The label warns that all insulins shift potassium into cells and can cause low blood potassium. It gives no rate.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The glargine label states that all insulins cause a shift in potassium from outside to inside cells, possibly leading to hypokalemia, and that untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia and death. It names people on potassium-lowering medicines as at risk [5].
Population: A class warning in labeling, with no study counts [5].
Sources: [5]
Caveats: The label gives no numbers.

LimitedHow often is not known

Fluid retention and heart failure with thiazolidinediones

The label warns that thiazolidinedione diabetes drugs taken with insulin can cause dose-related fluid retention, which may lead to or worsen heart failure.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The glargine label states that thiazolidinediones can cause dose-related fluid retention when used with insulin, and that this may lead to or exacerbate heart failure. It also states that some people on insulin have had sodium retention and edema, particularly when poor control was improved by intensified treatment [5]. In a 5-year trial, peripheral edema was reported by 20.0% on glargine and 22.7% on NPH insulin [5].
Population: A class warning in labeling. The edema rates come from 1,017 adults with type 2 diabetes [5].
Sources: [5]
Caveats: The label gives no rate for heart failure. The edema rates compare two insulins, with no group off insulin.

LimitedHow often is not known

Other medicines that raise the chance of low blood sugar

The label lists other diabetes drugs, ACE inhibitors, angiotensin receptor blockers, fluoxetine, MAO inhibitors, salicylates and sulfonamide antibiotics as drugs that may raise the risk of low blood sugar.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The glargine label lists drugs that may increase the risk of hypoglycemia: antidiabetic agents including GLP-1 receptor agonists, DPP-4 inhibitors and SGLT-2 inhibitors, ACE inhibitors, angiotensin II receptor blockers, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs and sulfonamide antibiotics. It lists alcohol, beta-blockers, clonidine and lithium as able to raise or lower insulin's effect [5]. In empagliflozin trials, low glucose readings were more frequent when it was added to insulin [22].
Population: Drug lists in labeling, with no study counts [5].
Sources: [5], [22]
Caveats: The label gives no rates for these combinations.

LimitedHow often is not known

Medicines that weaken insulin's effect

The label lists corticosteroids, diuretics, estrogens, oral contraceptives, thyroid hormones, atypical antipsychotics and several other drugs as lowering the blood sugar effect of insulin.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The glargine label lists drugs that may decrease its blood glucose lowering effect: atypical antipsychotics such as olanzapine and clozapine, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens, protease inhibitors, somatropin, sympathomimetic agents such as albuterol, and thyroid hormones [5].
Population: Drug lists in labeling, with no study counts [5].
Sources: [5]
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 glargine label states that signs and symptoms of hypoglycemia may be reduced or absent in people taking antiadrenergic drugs such as beta-blockers, clonidine, guanethidine and reserpine [5].
Population: A statement in labeling, with no study counts [5].
Sources: [5]
Caveats: The label gives no rate.

LimitedHow often is not known

Allergic reactions

The label reports severe, life-threatening generalized allergy including anaphylaxis with insulin, and redness, itching and swelling at injection sites. It gives no rate.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The glargine label states that severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension and shock, has occurred with insulin. Local reactions included redness, pain, itching, hives, edema and inflammation [5]. The insulin aspart label describes local reactions as usually self-limiting [19].
Population: Trial and postmarketing reports summarized in labeling [5][19].
Sources: [5], [19]
Caveats: No denominator is given for generalized allergy.

LimitedHow often is not known

Ketoacidosis after insulin pump failure

The label warns that pump or infusion set failure can rapidly lead to high blood sugar and ketoacidosis. Trials found more ketoacidosis only where pumps were used.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The insulin aspart label states that malfunction of the insulin pump or infusion set, or insulin degradation, can rapidly lead to hyperglycemia and ketoacidosis [19]. In a Cochrane review of intensive glucose control in type 1 diabetes, the risk of ketoacidosis was raised only in studies that used insulin pumps in the intensive group [2].
Population: A warning in labeling [19]; 12 trials in type 1 diabetes [2].
Sources: [19], [2]
Caveats: Rated very low quality evidence, with no pooled rate [2]. Most of the trials date from the 1980s.

LimitedHow often is not known

Mix-ups between insulin products

The label reports medication errors after marketing in which rapid-acting and other insulins were given by accident in place of glargine.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The glargine label reports postmarketing medication errors in which rapid-acting insulins and other insulins were accidentally administered instead of glargine [5].
Population: Voluntary postmarketing reports [5].
Sources: [5]
Caveats: Reports with no denominator.

Checked, no increase found2

Limited

Cancer

One trial found no difference in cancers between insulin glargine and standard care over a median 6.2 years in 12,537 people.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Cancers did not differ between the glargine and standard care groups (HR 1.00, 95% CI 0.88 to 1.13) over a median 6.2 years [8].
Population: 12,537 people with cardiovascular risk factors and raised blood sugar or type 2 diabetes, mean age 63.5 [8].
Sources: [8]
Caveats: One manufacturer-funded trial of one insulin.
Why limited: This rests on one trial, of 12,537 people. Strength counts independent studies that agree, so one trial is limited at any size.

ModerateStudied in pregnancy

Pregnancy

Not linked to more harm to the baby with glargine than with NPH insulin in pregnancy, in two meta-analyses of mostly observational studies.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Across eight studies of women with diabetes in pregnancy, fetal outcomes did not differ significantly between insulin glargine and NPH insulin [23]. A second meta-analysis of 24 studies found similar birth weights, severe maternal hypoglycemia and neonatal intensive care admission with glargine and NPH, and similar outcomes with aspart and regular insulin. Lispro was associated with higher birth weight and more large-for-gestational-age births than regular insulin (RR 1.42) and with less severe maternal hypoglycemia (RR 0.33) [24]. The glargine label states that published studies have not reported a clear association with adverse developmental outcomes, and that poorly controlled diabetes in pregnancy carries risks to mother and fetus [5].
Population: 702 women with pregestational or gestational diabetes in eight studies [23]; 3,734 women in 24 studies [24].
Sources: [23], [24], [5]
Caveats: Mostly observational studies comparing one insulin with another. The label gives the background risk of major birth defects as 6% to 10% in women with pregestational diabetes and an HbA1c above 7 around conception [5].

Claims tested and not found

That insulin glargine raises cancer risk. In 12,537 people followed a median 6.2 years, cancers did not differ between glargine and standard care (HR 1.00, 95% CI 0.88 to 1.13) [8].
That insulin treatment prevents heart attacks or lengthens life in type 2 diabetes. Cardiovascular outcomes did not differ between glargine and standard care (HR 1.02, 95% CI 0.94 to 1.11) [8], and across 20 trials insulin did not change death from any cause (RR 0.99, 95% CI 0.92 to 1.06) [7].
That long-acting analogs lower HbA1c more than NPH insulin. Cochrane reviews found comparable HbA1c in type 2 diabetes [10] and a mean difference of 0.01% between detemir and NPH in type 1 diabetes [11].
That rapid-acting analogs control type 2 diabetes better than regular human insulin. Across 9 trials, HbA1c change did not differ (mean difference -0.03%, 95% CI -0.16 to 0.09) [15].
That glargine in pregnancy harms the baby more than NPH insulin. Across eight studies of 702 women, fetal outcomes did not differ significantly [23].

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Semlitsch T, Engler J, Siebenhofer A, et al. (Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus. Cochrane Database of Systematic Reviews. 2020. https://doi.org/10.1002/14651858.CD005613.pub4
Hemmingsen B, Metzendorf MI, Richter B. (Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus. Cochrane Database of Systematic Reviews. 2021. https://doi.org/10.1002/14651858.CD013498.pub2
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Fullerton B, Siebenhofer A, Jeitler K, et al. Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus. Cochrane Database of Systematic Reviews. 2016. https://doi.org/10.1002/14651858.CD012161
Fullerton B, Siebenhofer A, Jeitler K, et al. Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus. Cochrane Database of Systematic Reviews. 2018. https://doi.org/10.1002/14651858.CD013228
Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. New England Journal of Medicine. 2005. https://doi.org/10.1056/NEJMoa052187
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U.S. Food and Drug Administration. NovoLog (insulin aspart) injection, prescribing information (Novo Nordisk). 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3a1e73a2-3009-40d0-876c-b4cb2be56fc5
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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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