The injectable glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Wegovy), which was approved by the FDA in 2021 for chronic weight management in adults, has now been approved for chronic weight management in children ≥12 years old with an initial BMI in the ≥95th percentile for age and sex.Semaglutide is also available as Ozempic and Rybelsus for treatment of type 2 diabetes in adults.

Diet, exercise, and weight loss can improve glycemic control, but almost all patients with type 2 diabetes require antihyperglycemic drug therapy. Treating to a target A1C of <7% while minimizing hypoglycemia is recommended to prevent microvascular complications of diabetes (retinopathy, nephropathy, and neuropathy). An A1C target of <8% may be appropriate for some older patients.

Diet, exercise, and weight loss can improve glycemic control, but almost all patients with type 2 diabetes eventually require drug therapy. Treating to a glycated hemoglobin (A1C) concentration of <7% can prevent microvascular complications (retinopathy, nephropathy, and neuropathy), but whether it prevents macrovascular complications and death is unclear. An A1C target of <8% may be appropriate for older patients and those with underlying cardiovascular disease (CVD), a history of severe hypoglycemia, diabetes-related complications, a limited life expectancy, or a long duration of disease.

An oral formulation of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Rybelsus – Novo Nordisk) has been approved by the FDA for once-daily treatment of type 2 diabetes in adults. Semaglutide, which has been available in a subcutaneously-injected formulation (Ozempic) since 2017, is the first GLP-1 receptor agonist to become available for oral administration; the 4 other GLP-1 receptor agonists currently available in the US are administered by subcutaneous (SC) injection.

Since 2008, because of safety concerns, the FDA has mandated that long-term cardiovascular outcomes trials be conducted for all new drugs for type 2 diabetes. Reductions in the incidence of macrovascular complications in these trials with some sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists in patients at risk for cardiovascular disease (see Table 1) have led to new recommendations.

The FDA has approved semaglutide (Ozempic – Novo Nordisk), a long-acting injectable GLP-1 (glucagon-like peptide-1) receptor agonist, for once-weekly treatment of adults with type 2 diabetes. It is the sixth GLP-1 receptor agonist to be approved in the US.

The motor symptoms of Parkinson's disease (PD) are caused primarily by degeneration of dopaminergic neurons in the substantia nigra. The nonmotor symptoms of the disease are thought to be caused by degeneration of other neurotransmitter systems.

For many years, the goal of drug therapy for most patients with type 2 diabetes has been to achieve and maintain an A1C of <7%. Achieving that goal can prevent microvascular complications (diabetic retinopathy, nephropathy, neuropathy), but whether it prevents macrovascular complications (myocardial infarction [MI], stroke) has been less clear. The FDA now requires that cardiovascular safety studies be performed for all new drugs for type 2 diabetes.1 Recent findings that some of the newer second-line drugs for type 2 diabetes have cardiovascular benefits have led to new interest in the cardiovascular efficacy and safety of all antidiabetic drugs.

The FDA has approved lixisenatide (Sanofi), a short-acting injectable GLP-1 (glucagon-like peptide-1) receptor agonist, for once-daily treatment of adults with type 2 diabetes, both alone (Adlyxin) and in a fixed-ratio combination with insulin glargine (Soliqua 100/33). Lixisenatide has been available since 2013 in many other countries as Lyxumia. It is the fifth GLP-1 receptor agonist to be approved in the US.

The goal of drug therapy for type 2 diabetes is to achieve and maintain a near-normal glycated hemoglobin (A1C) concentration without inducing hypoglycemia; the target is generally an A1C of ≤7%. Treating to this target has been shown to prevent microvascular complications (retinopathy, nephropathy, and neuropathy), but whether it prevents macrovascular outcomes is unclear. An A1C target of <8% may be appropriate for older patients and those with underlying cardiovascular disease, a history of severe hypoglycemia, diabetes-related complications or comorbidities, or a long duration of disease.

Adults with a body mass index (BMI) between 25 and 29.9 kg/m² are considered overweight. Those with a BMI ≥30 are considered obese. Losing even a small amount of weight and increasing physical activity can prevent some of the complications of obesity, particularly type 2 diabetes. Diet and exercise are the preferred methods for losing weight, but long-term failure rates are high. Several drugs have been approved by the FDA for weight reduction, but adherence is poor, adverse effects are common, and patients usually regain the lost weight when the drug is stopped. Bariatric surgery can produce substantial weight loss and significantly reduce obesity-related comorbidities; long-term data on its safety are encouraging, but still limited. Guidelines for the management of overweight or obese adults have recently been published.

Two new injectable GLP-1 (glucagon-like peptide-1) receptor agonists, dulaglutide (Trulicity [trū li si tee] – Lilly) and albiglutide (Tanzeum [tan' zee um] – GSK), have been approved by the FDA for once-weekly treatment of type 2 diabetes. Other available GLP-1 receptor agonists include exenatide, which is approved for injection twice daily (Byetta) or once weekly (Bydureon), and liraglutide (Victoza), which is injected once daily.

The goal of drug therapy for type 2 diabetes is to achieve and maintain a near-normal A1C concentration without inducing hypoglycemia; the target is generally an A1C of <7.0%. Treating to this target has been shown to prevent the microvascular complications of retinopathy and nephropathy, but whether it prevents macrovascular outcomes remains unclear. Three large trials found that intensive glucose control did not reduce the incidence of macrovascular events. One of these trials (ACCORD) in >10,000 patients with type 2 diabetes, with or at high-risk for cardiovascular disease, found that treating patients intensively with antihyperglycemic drugs to an A1C target of 6.0% for a mean of 3.7 years did not significantly reduce the incidence of major cardiovascular events (the primary endpoint) and was associated with increased all-cause mortality compared to patients treated to an A1C target of 7.0-7.9%. An A1C target of 7-8% may be prudent in older patients and in those with underlying cardiovascular disease, severe hypoglycemia, or multiple diabetes-related complications or co-morbidities.

Canagliflozin (kan" a gli floe' zin; Invokana – Janssen), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has been approved by the FDA for oral treatment of type 2 diabetes.

Most experts agree that lifestyle modifications and metformin (Glucophage, and others) should be used first to treat patients with type 2 diabetes. If metformin alone fails to control hyperglycemia, there is no general agreement on which drug should be added next. A recent article in The Medical Letter offered some support for a sulfonylurea. Three recent trials published in The Lancet favored the long-acting basal insulin glargine, the glucagon-like peptide (GLP-1) analog exenatide, and the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin, respectively. Some of the advantages and disadvantages of these and other available agents are listed in Table 1 on the opposite page.

The FDA has approved a once-weekly extendedrelease formulation of exenatide (Bydureon – Amylin), an injectable glucagon-like peptide-1 (GLP-1) receptor agonist, for treatment of type 2 diabetes.

Liraglutide (Victoza – Novo Nordisk), a glucagon-like peptide-1 (GLP-1) receptor agonist given by subcutaneous injection, has been approved by the FDA for treatment of patients with type 2 diabetes. It can be used alone or in addition to oral antidiabetic drugs such as metformin (Glucophage, and others) or glimepiride (Amaryl, and others). Liraglutide is not recommended for first-line therapy and is not approved for use with insulin.