From the Guidelines
Oral semaglutide can be used in patients with impaired renal function, including those with chronic kidney disease (CKD), without dose adjustment. The medication is primarily metabolized by proteolytic cleavage of the peptide backbone and beta-oxidation of the fatty acid side chain, rather than being eliminated through the kidneys 1. According to the most recent evidence, no specific dose modifications are required for patients with mild, moderate, or severe renal impairment, including those with end-stage renal disease 1. However, patients with renal impairment may experience more gastrointestinal side effects, so careful monitoring is recommended. Key points to consider when prescribing oral semaglutide to patients with CKD include:
- Starting with the standard initial dose of 3 mg once daily for 30 days, then increasing to 7 mg once daily
- If needed, increasing the dose to the maximum of 14 mg once daily after at least 30 days on the 7 mg dose
- Taking oral semaglutide on an empty stomach with no more than 4 ounces of plain water, at least 30 minutes before the first food, beverage, or other oral medications of the day to ensure proper absorption
- Monitoring patients for gastrointestinal reactions and changes in kidney function, particularly in those with CKD. It is essential to weigh the benefits of oral semaglutide, including its potential to reduce albuminuria and slow eGFR decline, against the potential risks and side effects in patients with CKD 1.
From the FDA Drug Label
Based on a population pharmacokinetic analysis, age, sex, race, and ethnicity, and renal impairment do not have a clinically meaningful effect on the pharmacokinetics of semaglutide Patients with Renal impairment - Renal impairment does not impact the pharmacokinetics of semaglutide in a clinically relevant manner. This was shown in a study with a single dose of 0. 5 mg semaglutide in patients with different degrees of renal impairment (mild, moderate, severe, ESRD) compared with subjects with normal renal function.
Oral Semaglutide can be given to a patient with impaired renal function (Chronic Kidney Disease, CKD), as renal impairment does not have a clinically meaningful effect on the pharmacokinetics of semaglutide 2.
From the Research
Oral Semaglutide in Patients with Impaired Renal Function
The use of oral semaglutide in patients with chronic kidney disease (CKD) has been investigated in several studies.
- A retrospective cohort study 3 found that oral semaglutide was tolerated by most individuals with CKD 4 or greater, despite associated gastrointestinal side effects, and led to an improvement in glycemic control and insulin discontinuation in patients with type 2 diabetes mellitus (T2DM).
- A phase 3a trial 4 demonstrated the efficacy and safety of oral semaglutide in patients with T2D and moderate renal impairment, with significant reductions in HbA1c and body weight.
- A review of data from several trials 5 found that oral semaglutide was effective in patients with T2D and cardiovascular disease, renal impairment, or other comorbidities, and in older patients, with no requirements for dose adjustment.
- A real-world study 6 compared the effectiveness of subcutaneous versus oral semaglutide formulations in patients with CKD and T2DM, and found that oral semaglutide significantly reduced HbA1C and BMI, with similar gastrointestinal side effects to the subcutaneous formulation.
- Another real-world study 7 found that subcutaneous semaglutide improved glycemic control and decreased weight in patients with T2D and CKD, with a significant decrease in albuminuria in patients with macroalbuminuria.
Key Findings
- Oral semaglutide is effective in improving glycemic control and reducing body weight in patients with T2D and CKD.
- The safety profile of oral semaglutide is consistent with the GLP-1 receptor agonist class, with gastrointestinal adverse events most commonly reported.
- Oral semaglutide can be used in patients with moderate renal impairment, with no requirements for dose adjustment.
- The efficacy and safety of oral semaglutide in patients with CKD and T2D are similar to those of the subcutaneous formulation.
Patient Considerations
- Patients with CKD and T2D may benefit from treatment with oral semaglutide, with significant improvements in glycemic control and weight loss.
- Gastrointestinal side effects are common, but can be managed with appropriate monitoring and dose adjustment.
- Oral semaglutide may be a suitable alternative to subcutaneous semaglutide in patients with CKD and T2D, with similar efficacy and safety profiles.