Antidiabetic Agents: Generic and Brand Names
- Alpha-glucosidase inhibitors
- acarbose miglitol (Precose, Glyset)
- Biguanides
- metformin (Glucophage)
- Dipeptidyl peptidase-4-inhibitors
- linagliptin (Tradjenta)
- saxagliptin (Onglyza)
- sitagliptin (Januvia)
- Human amilyn
- pramlintide acetate (Symlin)
- Incretin mimetics
- exanatide (Baraclude)
- liraglutide (Victoza)
- Meglitinides
- nateglinide (Starlix)
- repaglinide (Prandin)
- Thiozolidinediones
- pioglitazone (Actos)
- rosiglitazone (Avandia)
Therapeutic Action
Alpha-glucosidase inhibitors (acarbose, miglitol) block alpha-glucosidase, the enzyme that breaks glucose down for absorption, so they delay glucose absorption. Their effect on glucose is mild and they do not enhance insulin secretion, but they carry a risk of severe hepatic toxicity and GI distress. The biguanide metformin decreases glucose production and increases glucose uptake. It lowers blood glucose effectively without causing the hypoglycemia sulfonylureas do, but it carries an FDA boxed warning for metformin-associated lactic acidosis, a rare but potentially fatal complication whose risk rises with renal impairment, dehydration, heart failure, excess alcohol, hepatic impairment, or sepsis (metformin prescribing information, DailyMed). Meglitinides (nateglinide, repaglinide) act like sulfonylureas to increase insulin release.
Synthetic human amylin (pramlintide) modulates gastric emptying after a meal to produce satiety and blocks the postmeal glucagon rise that normally elevates glucose. Amylin is a hormone made by pancreatic beta cells that helps regulate postmeal glucose. Do not use it in a patient who cannot eat. Incretin mimetics (exenatide, liraglutide) mimic GLP-1: glucose-dependent insulin secretion by the beta cells, suppression of elevated glucagon, and slowed gastric emptying. DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin) slow the breakdown of GLP-1 to prolong those same effects. Thiazolidinediones (pioglitazone, rosiglitazone) decrease insulin resistance.
Indications
Metformin is approved for children 10 years of age and older and is also used to treat women with polycystic ovarian syndrome (PCOS). Meglitinides are rapid-acting with a very short half-life, so they target postprandial glucose and are taken just before meals. Thiazolidinediones are combined with insulin, metformin, and sulfonylureas in patients with insulin resistance. Bromocriptine, a dopamine agonist used for Parkinson's disease, was approved in 2009 as a CNS approach to type 2 diabetes.
Pharmacokinetics
Here are the characteristic interactions of other antidiabetic agents and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Oral | Slow | 2-2.5 h | 10-16 h |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 6.2 h and then 17 h | liver | urine |
Contraindications and Cautions
Allergy to sulfonylureas or other antidiabetic agents (avoid hypersensitivity reactions). Type 1 diabetes, where there are no functioning beta cells for the drug to act on. Pregnancy and lactation, for potential adverse effect on the fetus or neonate.
Adverse Effects
Common effects include hypoglycemia, lactic acidosis, GI upset, nausea, anorexia, diarrhea, heartburn, and allergic skin reaction. Pioglitazone use beyond 1 year is associated with a roughly 20% to 40% increased risk of bladder cancer, and the FDA advises against starting or continuing it in patients with active bladder cancer (FDA Drug Safety Communication). Rosiglitazone is linked to increased cardiovascular risk.
Interactions
Decreased excretion with drugs that acidify urine.
Nursing Considerations
Nursing considerations are the same as for sulfonylureas.
Frequently Asked Questions
Which antidiabetic agent carries the highest risk of lactic acidosis?
Metformin. It has an FDA boxed warning for metformin-associated lactic acidosis. The risk climbs with renal impairment, dehydration, acute heart failure, heavy alcohol use, hepatic impairment, or sepsis, so check renal function before and during therapy.
Why does metformin not cause hypoglycemia the way sulfonylureas do?
Metformin decreases hepatic glucose production and increases glucose uptake rather than forcing insulin release. Because it does not push extra insulin into the blood, it rarely causes hypoglycemia on its own, though hypoglycemia can occur when it is combined with insulin or a sulfonylurea.
What is the bladder cancer concern with pioglitazone?
Pioglitazone use beyond one year is associated with about a 20% to 40% higher risk of bladder cancer. The FDA advises against starting it in patients with active bladder cancer and weighing the risk in anyone with a history of it.
Can pramlintide be given to a patient who is not eating?
No. Pramlintide (synthetic amylin) slows gastric emptying and blunts the postmeal glucagon rise, so it is tied to meals. Do not give it to a patient who cannot eat, because of hypoglycemia risk.
Which classes target postprandial (after-meal) glucose specifically?
Meglitinides (nateglinide, repaglinide) are rapid acting with a very short half-life and are taken just before meals to blunt the postmeal spike. Alpha-glucosidase inhibitors (acarbose, miglitol) also act mainly on after-meal glucose by delaying carbohydrate absorption.