Antidiabetics
Drugs used to treat diabetes: Antidiabetic medications are used to treat diabetes. They include insulin and oral hypoglycemics, which help control blood glucose levels.
Insulin: Insulin is an injectable medication that lowers blood glucose levels. It’s usually administered subcutaneously; only regular insulin can be given intravenously. Insulin comes in multiple forms that differ in onset (how quickly they start working) and duration (how long they last). The most common adverse effect is hypoglycemia (low blood sugar). Other adverse effects include weight gain, hypersensitivity reactions, and lipodystrophy. Lipodystrophy causes fatty swellings or lumps at insulin injection sites. Insulin is the only medication available to lower blood glucose levels in people with type 1 diabetes.
Rapid acting insulins: These have an onset of action within 5-30 minutes and last up to 4 hours. Examples include lispro insulin (Humalog), aspart insulin (Novolog), glulisine (Apidra), and inhaled technosphere insulin (Afrezza).
Short acting insulins: These have an onset of action within 1 hour and last about 5-8 hours. Examples include regular human insulin (Humulin R, Novolin R).
Intermediate acting insulins: These have an onset of action within 2 hours and last about 12-16 hours. Examples include NPH (neutral protamine Hagedorn) or isophane insulin (Humulin N, Novolin N).
Long acting or basal insulins: These have an onset of action within 2-4 hours and last 24-42 hours. Examples include detemir (Levemir), glargine (Lantus, Basaglar), and degludec (Tresiba).
Insulin mixtures: Many products combine insulins to help regulate blood glucose (for example, a faster-acting insulin with a longer-acting insulin). Examples include Humalog Mix 50/50 (lispro insulin and insulin lispro protamine), Humulin 70/30 (isophane insulin and regular insulin), and Novolog Mix (insulin aspart protamine and insulin aspart). The numbers show the percentage of each insulin type in the mixture. For example, 70/30 means 70% of one insulin type is mixed with 30% of another.
Oral hypoglycemics: Oral hypoglycemic agents (OHAs) are oral drugs used to manage diabetes mellitus. There are several classes of OHAs, described below.
Metformin (biguanide): Metformin lowers blood glucose by decreasing intestinal absorption of glucose. It also improves insulin sensitivity. It’s commonly used for pre-diabetes and type 2 diabetes to lower HbA1c levels. It’s also used in polycystic ovarian syndrome (PCOS), which is often associated with pre-diabetes. Common brands include Glucophage, Glumetza, Fortamet, and Riomet. Adverse effects include lactic acidosis, metallic taste in the mouth, vitamin B12 deficiency, nausea, vomiting, diarrhea, abdominal pain, muscle cramps, and mental status changes. Metformin should be discontinued before surgery or administration of contrast media to reduce the risk of lactic acidosis.
Sulfonylureas: Sulfonylureas are oral hypoglycemics that lower blood sugar by blocking ATP-sensitive K+ channels (KATP) on pancreatic beta cells, which triggers insulin secretion. For this reason, they’re also called insulin secretagogues. Adverse effects include hypoglycemia, weight gain, decreased white blood cell count, skin allergies, and alcohol intolerance. They’re contraindicated in sulfa allergies and in advanced renal or hepatic failure. Use caution when co-prescribing beta blockers, which can mask signs of hypoglycemia such as tachycardia and tremors. Examples include glipizide (GlipiZIDE XL, Glucotrol), glimepiride (Amaryl), and glyburide (DiaBeta, Glynase).
Thiazolidinediones: Thiazolidinediones activate the transcription factor PPAR gamma, increasing transcription of genes involved in glucose metabolism. They increase insulin sensitivity. Adverse effects include weight gain, edema, fluid retention, heart failure, and osteoporosis. Examples include pioglitazone (Actos) and rosiglitazone (Avandia). They’re contraindicated in patients with severe heart failure.
Meglitinides: Like sulfonylureas, meglitinides increase insulin secretion from pancreatic beta cells by blocking K+ channels. Adverse effects include weight gain, hypoglycemia, and hepatotoxicity. Examples include repaglinide (Prandin) and nateglinide (Starlix).
Incretin mimetics or GLP 1 receptor agonists: These drugs bind to GLP 1 receptors, increasing insulin secretion and slowing gastric emptying. They mimic incretin hormones naturally produced in the body that increase insulin secretion. They cause weight loss. Adverse effects include GI upset, pancreatitis, and rarely, pancreatic cancer. Examples include liraglutide (Victoza, Saxenda), semaglutide (Ozempic, Wegovy), tirzepatide (Mounjaro), dulaglutide (Trulicity), and exenatide (Bydureon).
DPP 4 (dipeptidyl peptidase) inhibitors or gliptins: These drugs enhance the effect of incretin GLP 1 by inhibiting the DPP 4 enzyme that degrades GLP 1. This increases insulin secretion and delays gastric emptying. Adverse effects include GI upset, diarrhea, constipation, nasopharyngitis, URTI, arthralgia, headache, dizziness, pancreatitis, and acute renal failure. Examples include sitagliptin (Januvia), linagliptin (Tradjenta), saxagliptin (Onglyza), and alogliptin (Nesina).
SGLT 2 inhibitors: These drugs inhibit SGLT 2 (sodium dependent glucose cotransporter) in the proximal tubule of the kidney, decreasing renal glucose reabsorption and lowering blood glucose levels. They promote weight loss. Adverse effects include UTIs, vulvovaginitis (especially candidal), dehydration, and diabetic ketoacidosis. Examples include dapagliflozin (Farxiga), empagliflozin (Jardiance), and canagliflozin (Invokana).
Alpha glucosidase inhibitors: These drugs inhibit the enzyme alpha glucosidase, which breaks down glucose, thereby decreasing glucose absorption. Adverse effects include gas, bloating, flatulence, abdominal discomfort, and diarrhea. They shouldn’t be used in inflammatory bowel disease and malabsorption syndromes. Examples include acarbose (Precose) and miglitol (Glyset).
Amylin analogue: This drug slows gastric emptying by activating amylin receptors in the brain and acts on the hypothalamus to decrease appetite. It reduces the postprandial rise in blood glucose and causes weight loss. An adverse effect is hypoglycemia. The only available drug in this class is pramlintide (Symlin).
Antidiabetic combinations: Combination antidiabetics contain drugs from two or more classes with different mechanisms of action. These combinations can improve compliance and increase efficiency.
| Drugs in combination | Brand names |
|---|---|
| Sitagliptin and metformin | Janumet, Janumet XR |
| Canagliflozin and metformin | Invokamet |
| Empagliflozin and linagliptin | Glyxambi |
| Empagliflozin and metformin | Synjardy, Synjardy XR |
| Metformin and saxagliptin | Kombiglyze XR |
| Glyburide and metformin | Glucovance |
| Empagliflozin, linagliptin, and metformin | Trijardy XR |