What is the effect of Sitagliptin (Januvia)?

From the Guidelines

Januvia (sitagliptin) is a suitable option for treating type 2 diabetes, with a standard dose of 100 mg once daily, although patients with kidney problems may require lower doses (50 mg or 25 mg daily) as indicated in the 2022 consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1.

Key Points to Consider

• Januvia works by increasing incretin hormones that stimulate insulin release after meals and reduce glucagon production, which helps lower blood glucose without causing hypoglycemia when used alone.
• It can be taken with or without food and is often prescribed alongside other diabetes medications like metformin or used as monotherapy.
• Common side effects include upper respiratory infections, headache, and occasionally joint pain.
• Patients should monitor their blood sugar regularly while taking Januvia and report any unusual symptoms to their healthcare provider.
• Unlike some diabetes medications, Januvia is weight-neutral and doesn't typically cause hypoglycemia when used by itself, making it a good option for many patients with type 2 diabetes who need additional blood sugar control.

Important Considerations

• The dose of Januvia needs to be adjusted based on renal function, with a maximum dose of 50 mg daily for patients with an estimated glomerular filtration rate (eGFR) of 30-44 mL/min/1.73 m2 and a maximum dose of 25 mg once daily for patients with an eGFR of 15-29 mL/min/1.73 m2, as per the 2022 ADA and KDIGO consensus report 1.
• Rare but increased rates of pancreatitis and musculoskeletal side effects have been reported with the use of DPP-4 inhibitors, including Januvia, as noted in the 2018 management of hyperglycemia in type 2 diabetes consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) 1.
• Cardiovascular outcomes trial data for the DPP-4 inhibitors, including sitagliptin, showed no statistically significant differences in rates of major cardiovascular events between treatment and placebo groups, as mentioned in the 2017 pharmacologic therapy for type 2 diabetes synopsis by the American Diabetes Association standards of medical care in diabetes 1.

From the FDA Drug Label

History of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema. [See Warnings and Precautions (5.4); Adverse Reactions (6.2).] The main concern with Januvia (sitagliptin) is a history of serious hypersensitivity reactions, including:

• Anaphylaxis
• Angioedema 2

From the Research

Januvia Overview

• Januvia, also known as sitagliptin, is an orally administered, potent and highly selective inhibitor of dipeptidyl peptidase-4 (DPP-4) 3.
• It is approved for use in the management of adults with type 2 diabetes mellitus, and has been shown to be effective in improving glycaemic control in patients with type 2 diabetes 3, 4.

Efficacy and Safety

• Numerous randomized placebo- or active comparator-controlled trials have demonstrated the efficacy of sitagliptin in terms of improving glycaemic control in patients with type 2 diabetes 3.
• Sitagliptin has been shown to be generally well tolerated, with a low risk of hypoglycaemia and a neutral effect on body weight 3, 4.
• The primary endpoint of the clinical trials was the reduction from baseline in glycosylated haemoglobin (HbA1c), although sitagliptin also showed beneficial effects for other endpoints, such as the proportion of patients who achieved target HbA1c, and reductions from baseline in fasting plasma glucose (FPG) levels and 2-h postprandial glucose (PPG) levels 3.

Special Populations

• Sitagliptin has been shown to be effective and safe in patients with type 2 diabetes and moderate to severe renal insufficiency, including patients with end-stage renal disease (ESRD) on dialysis 5.
• Sitagliptin has also been shown to be effective and safe in the inpatient management of general medicine and surgery patients with type 2 diabetes 6.

Potential Adverse Events

• Despite concerns regarding a possible increased risk of rare pancreatic adverse events (e.g. pancreatitis) with glucagon-like peptide-1 (GLP-1)-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, no causal association has been found 3, 4.
• Regulators in Europe have conducted a review of available data, concluding that there is little evidence that these drugs could cause pancreatic inflammation or pancreatic cancer 3.