| Comparison of diabetes treatment complications and therapeutic considerations |
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| Medication Class Drug Examples |
Dose-Adjustment Considerations |
Weight Effect |
CV Effects |
Bone Effect |
Association with Cancer |
Pregnancy Category |
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| Biguanide |
Renal insufficiency |
Neutral or loss |
Neutral or possible benefit on lipid profile and CV outcomes |
Neutral or possible benefit |
Possible beneficial effects |
B |
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| Metformin |
Hepatic insufficiency |
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| Thiazolidinedione |
Caution: CHF (class I and II) |
Gain and edema |
Increased risk of CHF; rosiglitazone associated with higher risk of ischemia and CV mortality |
Negative impact on BMD; increased fracture risk in select populations |
Pioglitazone associated with increased risk of bladder cancer |
C |
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| Rosiglitazone |
Contraindication: CHF (class III and IV); concurrent use of CYP2C8 inhibitors |
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| Pioglitazone |
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| Sulfonylurea |
Renal insufficiency (chlorpropamide, glyburide) |
Neutral or gain |
Increased risk of CV death following myocardial infarction |
No effect |
Unknown |
C (glyburide, class B) |
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| Chlorpropamide, tolbutamide |
Hepatic insufficiency |
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| Glyburide, glipizide, glimepiride |
Elderly or malnourished |
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| Meglitinide analogues |
Renal insufficiency |
Neutral or gain |
No change in lipids or blood pressure |
Unknown |
Unknown |
C |
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| Nateglinide |
Hepatic insufficiency |
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| Repaglinide |
Concomitant use with gemfibrozil (repaglinide) |
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Monitor with concurrent CYP3A4 metabolized medications |
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| α-Glucosidase inhibitors |
Renal insufficiency (acarbose, miglitol) |
Neutral |
Risk reduction for myocardial infarction and hypertension |
Unknown |
Unknown |
B |
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| Acarbose |
Hepatic insufficiency |
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| Miglitol |
Contraindication: cirrhosis, inflammatory bowel disease, colonic ulceration or obstruction |
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| Voglibose |
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| GLP-1r agonist |
Renal insufficiency (long-acting exenatide) |
Loss or neutral |
Beneficial, improves blood pressure and lipid profiles |
No effect |
Black-box warning for personal or family history of medullary thyroid cancer or MEN 2 |
C |
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| Exenatide |
Hepatic insufficiency (liraglutide) |
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| Liraglutide |
Contraindicated with prior pancreatitis |
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| DPP-4 analogues |
Renal insufficiency (saxagliptin, alogliptin) |
Neutral |
Neutral, possible beneficial effects on lipid profiles |
Decreased fractures |
Unknown |
B |
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| Saxagliptin |
Hepatic insufficiency |
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| Linagliptin |
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| Alogliptin |
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| Amylin analogues |
Reduce prandial insulin |
Neutral or loss |
Possible beneficial effect on lipid profiles |
Unknown |
Unknown |
C |
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| Pramlintide |
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| SGLT2 inhibitors |
Renal insufficiency |
Loss or neutral |
Beneficial effects on systolic blood pressure |
Unknown |
Unknown |
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| Canagliflozin |
Hepatic insufficiency |
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| https://pmc.ncbi.nlm.nih.gov/articles/PMC6533625/#fn-group1 |
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| Anti-Diabetic Drugs. The table provides an overview of oral and injectable non-insulin medications used to improve blood glucose levels. It includes the names of medication groups and specific drugs within each group, as well as information on their effects, side effects, and safety. (‘↑’Aggravation/increase, ‘↓’ improvement/decrease, |
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| Drug Group |
Specific Drug |
Effects |
Adverse Effects |
Safety |
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| Biguanides |
Metformin |
HbA1c ↓ |
Gastrointestinal disorders ↑ |
None |
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Body weight ↓→ |
Reversible vitamin B12 deficiency↑ |
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Cancer ↓? |
Lactic Acidosis ↑ |
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Cardiovascular↓? |
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| Glinides |
Repaglinide |
HbA1c ↓ |
Hypoglycemia ↑ |
None |
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Nateglinide |
Headache ↑ |
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Body weight ↑ |
Upper respiratory tract infection ↑ |
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| Alpha-Glucosidase inhibitors |
Acarbose |
HbA1c ↓ |
Gastrointestinal disorders ↑ |
None |
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Body weight ↓ → |
Serum transaminases (AST, ALT) ↑ |
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| SGLT2-I |
Empagliflozin |
HbA1c ↓ |
Diabetic ketoacidosis ↑ |
None |
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Dapagliflozin |
Body weight ↓ |
Genital infection ↑ |
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Canagliflozin |
BP ↓ |
Urinary tract infection ↑ |
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MACE ↓ |
Hypovolemia ↑ |
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Hospitalization for HF ↓ |
Acute kidney injury ↑ (related to hypovolemia) |
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Progression of renal disease ↓ |
Canagliflozin: |
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Amputation ↑ |
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Bone fracture ↑ |
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| Thiazolidineidiones |
Pioglitazone |
HbA1c ↓ |
Body weight ↑ |
Cancer? |
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BP ↓ |
Peripheral edema ↑ |
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NAFLD ↓ |
Anemia ↑ |
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MACE ↓ |
Hospitalization for HF ↑ |
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Bone fracture in women ↑ |
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| DPP-4 |
Sitagliotin |
HbA1c ↓ |
Saxagliptin: |
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Saxagliptin |
Hospitalization for HF? |
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Alogliptin |
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| Sulfonylureas |
Glimepiride |
HbA1c ↓ |
Body weight ↑ |
Glibenclamide |
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Gliclazide |
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Hypoglycemia ↑ |
Glipizide: |
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Glibenclamide |
Lack of durable effect |
Cardio-vascular events? |
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Glipizide |
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| GLP-1 RA |
Liraglutide Dulaglutide |
HbA1c ↓↓ |
Gastrointestinal disorders ↑ |
Pancreatitis |
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Semaglutide |
Body weight ↓ |
Bile stones |
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Orforglipron |
Systolic BP ↓ |
Semaglutide: |
Thyroid carcinoma |
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MACE ↓ |
Macular edema |
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Tirzepatide |
HF ? |
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| Combination therapy |
Retatrutide |
Quality of life for patients with HF (KCCQ-CSS) ↑ |
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NAFLD ↓ → |
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| https://www.mdpi.com/1422-0067/24/24/17147 |
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| Table Drug-induced hyperglycaemia and diabetes mellitus |
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| Pharmacological classes |
Main mechanisms |
Characteristics |
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| Drugs discussed in this review |
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| GCs |
Increase in hepatic glucose production (gluconeogenesis) |
Dose-dependent, rapid effect |
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Interference with multiple glucoregulatory pathways |
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| Antipsychotics |
Body weight gain |
Atypical (SGA > first generation) |
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Direct effects on insulin signalling and secretion |
Hierarchy among SGA |
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Dose-dependent |
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| ART |
Lipoatrophy, lipohypertrophy and insulin resistance |
Reduced toxicity with newer compounds |
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| ICIs |
Immune destruction of beta cells |
Partial similarities with type 1 diabetes |
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Risk of DKA |
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| Selected drugs not discussed in this review |
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| β-blockers |
Impaired insulin release |
Non-selective > β1-selective, long-term effect |
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| Diuretics |
Impaired insulin release (via hypokalaemia) |
Dose-dependent, thiazides > loop diuretics, long-term effect |
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Increased insulin resistance |
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| Calcineurin inhibitors |
Reduced insulin secretion |
Avoid in pancreas/beta cell transplantation |
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| Sexual steroids |
Increased insulin resistance |
Mainly those with androgenic component |
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| β2-adrenoreceptor agonists |
Increase hepatic glucose output |
Systemic administration, dose-dependent |
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| Somatostatin receptor agonists |
Reduced insulin secretion |
Rapid effect, mainly with pasireotide |
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| Statins |
Interference with multiple glucoregulatory pathways |
Dose- and time-dependent effect |
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| mTOR inhibitors |
Interference with the insulin signalling pathway |
Rapid and dose-dependent effect |
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| https://link.springer.com/article/10.1007/s00125-022-05666-w#Tab1 |
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