endocrine and metabolic disorders
Medications for Diabetes Mellitus Treatment
Oral Antihyperglycemic Medications
Oral antihyperglycemic medications (see table) are a mainstay of treatment for type 2 diabetes mellitus, along with injectableglucagon-like peptide-1 (GLP-1) receptor agonists. Oral antihyperglycemic medications may Enhance pancreaticinsulinsecretion (secretagogues) Sensitize peripheral tissues toinsulin(sensitizers) Impair gastrointestinal absorption of glucose Increase glycosuria Medications with different mechanisms of action may be synergistic. (See below for information on Glucagon-like peptide-1 (GLP-1) receptor agonists .) resistance and limit their usefulness. All also can cause Hypoglycemia . Risk factors include age also causes the Syndrome of Inappropriate ADH Secretion (SIADH) . Most patients taking sulfonylureas alone eventually require additional medications to achieve normoglycemia, suggesting that sulfonylureas may exhaust beta-cell function. However, worsening of Short-actinginsulinsecretagogues (repaglinide,nateglinide) stimulateinsulinsecretion in a manner similar to sulfonylureas. They are faster acting, however, and may stimulateinsulinsecretion more during meals than at other times. Thus, they may be especially effective for reducing postprandial hyperglycemia and appear to have lower risk of hypoglycemia. There may be some weight gain, although apparently less than with sulfonylureas. Patients who have not responded to other oral medications (eg, sulfonylureas,metformin) are not likely to respond to these medications. Biguanides (metformin) lower plasma glucose by decreasing hepatic glucose production (gluconeogenesis and glycogenolysis). They are considered peripheralinsulinsensitizers, but their stimulation of peripheral glucose uptake may simply be a result of reductions in glucose due to their hepatic effects. Biguanides also lower lipid levels and may also decrease gastrointestinal nutrient absorption and increase beta-cell sensitivity to circulating glucose.Metforminis the only biguanide commercially available in the United States. It is at least as effective as sulfonylureas in reducing plasma glucose, rarely causes hypoglycemia, and can be safely used with other medications andinsulin. In addition,metformindoes not cause weight gain and may even promote weight loss by suppressing appetite. However, the medication commonly causes gastrointestinal adverse effects (eg, dyspepsia, diarrhea), which for most people recede with time. Less commonly,metformincausesvitamin B12malabsorption, but clinically significant anemia is rare. to life-threatening Lactic Acidosis is very rare, but the medication is contraindicated in patients at risk of acidemia (including those with significant renal insufficiency, hypoxia or severe respiratory disease, alcohol use disorder, other forms of metabolic acidosis, or dehydration). The medication should be withheld during surgery, administration of IV contrast, and any serious illness. Many people receiving in reducing hemoglobin A1C. TZDs may be beneficial in treatment of Metabolic Dysfunction–Associated Liver Disease (MASLD) (MASLD; formerly nonalcoholic fatty liver disease [NAFLD]). , and may worsen Heart Failure (HF) in susceptible patients. Weight gain, due to fluid retention and increased adipose tissue mass, is common and may be substantial ( Alpha-glucosidase inhibitors (acarbose,miglitol) competitively inhibit intestinal enzymes that hydrolyze dietary carbohydrates; carbohydrates are digested and absorbed more slowly, thereby lowering postprandial plasma glucose. Alpha-glucosidase inhibitors are less effective than other oral medications in reducing plasma glucose, and patients often stop the medications because they may cause dyspepsia, flatulence, and diarrhea. But the medications are otherwise safe and can be used in combination with all other oral antihyperglycemic medications and withinsulin. secretion; prolonging its action thereby lowers plasma glucose. There is a slight increase in risk for Overview of Pancreatitis with DPP-4 inhibitors, but they are otherwise considered safe and well-tolerated. The hemoglobin A1C decrease is modest with DPP-4 inhibitors. , ertugiflozin) inhibit SGLT2 in the proximal tubule of the kidney, which blocks glucose reabsorption, thus causing glycosuria and lowering plasma glucose. SGLT2 inhibitors may also cause modest weight loss and lowering of blood pressure. SGLT-2 inhibitors decrease mortality, major adverse cardiovascular events, and heart failure hospitalizations in patients with an increased risk for cardiovascular disease. In addition SGLT-2 inhibitors prevent progression of Chronic Kidney Disease in patients with diabetes and reduced glomerular filtration rate or albuminuria. The most common adverse effects are genitourinary infections, especially mycotic infections. Orthostatic symptoms can also occur. SGLT-2 inhibitors can cause Diabetic Ketoacidosis (DKA) (DKA) in patients with either type 1 or type 2 diabetes, and ketoacidosis may occur at lower blood glucose levels than in other causes of DKA. Diagnosis of euglycemic DKA caused by SGLT-2 inhibitors is often delayed due to lower blood sugars. One large study showed an increase in lower limb amputation with Bromocriptineis adopamineagonist that lowers hemoglobin A1C about 0.5% by an unknown mechanism. Although approved for type 2 diabetes, it is not commonly used because of potential adverse effects. 1.Neal B, Perkovic V, Mahaffey KW, et al.Canagliflozinand Cardiovascular and Renal Events in Type 2 Diabetes.N Engl J Med2017;377(7):644-657. doi:10.1056/NEJMoa1611925 