What are the hypoglycemic drugs available for DM?

Hypoglycemic drugs for DM 

A number of groups of drugs are currently used for the treatment of diabetes mellitus (DM). In this post, in short, we will learn about the categories of drugs, mechanism of actions, important side effects and available medicines of each category with doses (except insulin).

Biguanides:

• Available medicine: Metformin [500mg, 850mg & 1000mg tab]
• Mechanism of action: Insulin sensitiser
• Starting dose is 500 mg BD. The maintenance dose is 1g BD.
• Gastrointestinal (diarrhoea, abdominal cramps, bloating and nausea) side effect is the main side effect

Sulphonylureas:

• Available medicine: Gliclazide [30mg, 60mg & 80mg], Glibenclamide [5mg], Glimepiride [1mg, 2mg, 3mg & 4mg] and Glipizide [2.5mg & 5mg].
• Mechanism of action: These are ‘insulin secretagogues’.
• Main side effects: weight gain, hypoglycemia.

Thiazolidinediones:

• Available medicine: Pioglitazone [15mg & 30mg].
• Mechanism of action: Enhance the action of endogenous insulin.
• Main side effects: Exacerbate cardiac failure by causing fluid retention, increased risk of bone fracture and bladder cancer.
• In combination with insulin, it can be very effective but markedly increases fluids retention and increases the risk of heart failure.
• It has a beneficial effect in reducing fatty liver and NASH.
• Increases weight

DPP-4 inhibitors:

• Available medicine: Sitagliptin [25mg, 50mg & 100mg], Vildagliptin [50mg], Saxagliptin [2.5mg & 5mg], Linagliptin [5mg] and Alogliptin.
• Mechanism of action: These drugs prevent the breakdown and therefore enhance the concentration of endogenous GLP-1 (glucagon-like peptide 1) and GIP (gastric inhibitory polypeptide). GLP-1 and GIP, both are incretin hormones, potentiate insulin secretion. DPP-4 (Dipeptidyl peptidase 4) break down these hormones rapidly.
• The Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin (TECOS) shows no adverse cardiovascular outcome for Sitagliptin.
• The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus –Thrombolysis in Myocardial Infarction (SAVOR­TIMI) study found an increased risk of heart failure in patients treated with Saxagliptin.

GLP-1 receptor agonists:

• Available medicine: Exenatide (twice daily), Exenatide modified release (once weekly), Liraglutide (once daily), Lixisenatide (once daily) and Albiglutide (once weekly).
• Mechanism of action: It is an incretin hormone and potentiates insulin secretion. It delays gastric emptying and, at the level of the hypothalamus, decreases appetite. Thus, GLP-1 lowers blood glucose and reduce weight.
• No oral preparation is available.  All are given via subcutaneous injections.
• The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) study has recently demonstrated that liraglutide, when added to usual therapy, results in improved cardiovascular outcomes over placebo in patients at high risk for cardiovascular disease.
• The Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) study, which showed that lixisenatide was neutral with respect to cardiovascular disease.
• Side effects: Nausea and increased risk of pancreatitis.

SGLT2 (the sodium and glucose transporter 2) inhibitors:

• Available medicines: Dapagliflozin [5mg & 10mg], Canagliflozin [100mg] and Empagliflozin[10mg & 25mg].
• Mechanism of action: Prevent the reabsorption of filtered glucose from the renal tubules (approximately 25% of the filtered glucose is not reabsorbed).
• Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA­REG Outcomes) trial showed that Empagliflozin therapy resulted in a 35% reduction in cardiovascular mortality and a similar reduction in admissions to hospital with heart failure.
• Candidates for SGLT2 inhibitors: Prior myocardial infarction, coronary artery disease, stroke, unstable angina or occlusive peripheral arterial disease.
• Side effects: Increased risk of genital fungal infection due to glycosuria.
• Complications: Euglycemic diabetic ketoacidosis (recognised but rare).
• Reduce weight

Meglitinide:

• Available medicine: Repaglinide [0.5mg, 1mg & 2mg] and nateglinide [120mg]
• Sulphonylureas like medicine.
• Increases weight

Alpha-glucosidase inhibitors:

• Available medicine: Acarbose [50mg & 100mg], miglitol [25mg & 50mg] and voglibose [200mcg and 300 mcg]
• Mechanism of action: Delay carbohydrate absorption in the gut by inhibiting disaccharidases. 
• Are taken with each meal and lower post-prandial blood sugar.
• Side effects: flatulence, abdominal bloating and diarrhoea.

 

Source: 

• Davidson's principles and practice of medicine 23rd Edition; page-746