CME INDIA Presentation by Dr. N. K. Singh, MD, FICP, Director, Diabetes and Heart Research Centre, Dhanbad, Jharkhand, India. Editor, www.cmeindia.in.
CME INDIA Discussion (08/04/2022)
Dr. Awadhesh K. Singh, DM Endo., Kolkata:
- On Semaglutide (Rybelsus) (3-7 mg) plus Dapa 10mg+Met 1 gm, one of my obese patients lost 9 Kg in 2 month (from 105 to 96 Kg now).
- OSA reduced dramatically. BP drugs reduced by half.
- Working good even better than RCT (though early trend). Switched one from Inj Dulaglutide to Rybelsus- lost further weight and even better glycaemic control.
- I had to stop in 1 in 20 total now. I use it sparingly who can afford (2-3 gold ring 💍 or diamond 💍 ring) 😜
Dr. Manoj Chawla, Diabetologist, Mumbai:
- I have a similar case of a young lady on cana met plus rybelsus 3–7 who has lost 10 kg in 2 months. DM for over 8 years.
- In fact I was a little apprehensive about GI side effects as saw that during oral sema RCT. Surprisingly most tolerating well up to 7 mg. Now some on 14 mg phase too.
“These experiences motivated to start Oral Semaglutide tab in few of my obese patient. Surprisingly in two months lost 3 kg and insulin dose drastically reduced and achieved euglycemia which was so erratic with insulin, gliclazide and Metformin. Never tolerated SGLT2 inhibitor due to genital mycotic infections. This patient was neither from higher income group, nor with a diamond ring. I was touched by her husband’s statement – spending one lac on jewellery is useless if a drug brings such benefits” – Dr. N. K. Singh (Editor).
Few Important FAQs
What is the clinical relevance of the dosing recommendations with oral Semaglutide?
- Food intake – prior dosing.
- Decreased – post-dosing fasting time.
- Increased – water volume.
What is SNAC & how it’s facilitating the absorption of oral formulation?
Credit: SNAC, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate. Buckley ST et al. Sci Transl Med 2018;10(467).
Why is 300 mg of SNAC co-formulated with all doses of oral semaglutide? Can oral semaglutide be broken to administer half dose?
- 300 mg of SNAC offers most optimum absorption
Should we be worried about– Pancreatitis, Retinopathy & other AEs with oral semaglutide?
- Oral semaglutide has not been studied in patients with history of pancreatitis.
- It seems safe to conclude that the phenomenon of early worsening of pre-existing Diabetic proliferative retinopathy was secondary to the initial and rapid improvement in glycemic control that occurred in SUSTAIN-6.
- Although current data argue against an increased risk of pancreatic cancer and thyroid cancer with semaglutide. (It can be debated whether the background incidence of these disorders is too low to fully conclude the absence of an association.)
What additional benefits beyond glycaemic control can be offered to patients initiated on oral Semaglutide?
- Oral Semaglutide achieved clinically significant weight reduction up to 5 kg.
- Significantly a greater number of patients achieved weight loss of ≥5% with oral semaglutide 14mg compared to placebo & comparators.
- More than 90% of the weight loss is accounted by the loss in whole body fat mass.
PIONEER 6: Cardio-vascular & all-cause mortality
- Promising CV safety with 21% MACE reduction for non-inferiority.
- Promising CV safety with 49% all-cause mortality & 51% CV death reduction for non-
- Inferiority.
- Pooled semaglutide data showed a significant reduction of 32% in risk of stroke compared with placebo.
GLP-1, glucagon-like peptide-1.Adapted from Drucker DJ. Cell Metab 2016:24:15–30; Muskiet MHA et al. Nat Rev Nephrol 2017;13:605–28.
Must educate your patients:
Credit: Am J Health Syst Pharm. 2021;78(7):556-567. doi:10.1093/ajhp/zxaa413(Ref-1)
Concomitant Medications can be at large safely given
Credit: Am J Health Syst Pharm. 2021;78(7):556-567. doi:10.1093/ajhp/zxaa413(ref-1)
What are the treatment recommendations in Hepatic and renal impairment? And should special consideration be given to elderly while dosing?
Hepatic
- No apparent effect of hepatic impairment, regardless of severity, on PK or tolerability of oral semaglutide.
- No dose adjustment of oral semaglutide is necessary in subjects with hepatic impairment.
Renal
- Renal impairment does not appear to impact PK properties of oral semaglutide.
- No dose adjustment of oral semaglutide is necessary in subjects with renal impairment.
Is it safe to use oral semaglutide with statins, B-blockers, anti-platelets & in patients with CVD?
- Oral semaglutide had no clinically relevant effect on exposure of all tested drugs.
Can oral semaglutide be used in subjects with upper GI disorders?
Is any dose modification required with oral semaglutide in patients on other oral anti-diabetic agents or insulin?
- When oral semaglutide is used in combination with metformin or SGLT-2I or TZD, no dose adjustment is required.
- A dose reduction may be required when used in combination with an SU or insulin due to an anticipated risk of hypoglycemia.
- A 20% reduction in total daily insulin dosage has been recommended when initiating oral semaglutide.
Quick Take-Aways
| Oral semaglutide should be taken on an empty stomach when the patient first wakes up. |
| Patients should take oral semaglutide with no more than a sip (up to 120 mL, or 4 fluid ounces) of plain water. |
| Patients should wait at least 30 minutes after taking oral semaglutide before consuming any food, other drinks, or other medica-tions. |
| It is best to eat within 30 to 60 minutes after taking oral semaglutide. |
| Oral semaglutide tablets must be kept in the blister card until use and therefore should not be placed in a pill box. |
| Oral semaglutide 7 mg is effective at lowering glycated hemoglobin (HbA1c), with estimated mean HbA1c reductions from baseline of approximately 0.9% to 1.2% after 26 weeks. If further HbA1c reductions are required, the patient can escalate the dose of oral semaglutide from 7 mg to 14 mg. |
| HbA1c reductions of approximately 1.0% to 1.4% can be expected with oral semaglutide 14 mg after 26 weeks, but as above, this can vary between patients. |
| Patients may lose an average of up to 2.2 to 2.4 kg after 26 weeks of treatment with oral semaglutide 7 mg, and up to 3.1 to 4.4 kg with oral semaglutide 14 mg. |
| Oral semaglutide has a favorable safety profile and is effective for patients with moderate renal impairment. |
| No dose adjustment of oral semaglutide is recommended in patients with renal impairment. |
| No dose adjustment of oral semaglutide is recommended in patients with hepatic impairment. Oral semaglutide does not affect exposure of lisinopril, warfarin, digoxin, or ethinylestradiol/levonorgestrel. |
| Oral semaglutide increases exposure of metformin, furosemide, and rosuvastatin; however, increases in exposure are not con- sidered to be clinically relevant. |
| Oral semaglutide increases exposure of levothyroxine. All drugs should be taken 30 min after oral semaglutide intake. Levothyroxine can be also taken at bed time with at least 3-hr gap after the dinner. |
| Patients should be informed that GI AEs can occur after initiating treatment with or escalating the dose of oral semaglutide, but that these events are generally mild-to-moderate and transient in nature. |
| Stop DPP-4Is while using oral semaglutide. |
| Oral semaglutide is not recommended during pregnancy. Potential risk to fetus. Breast feeding not recommended when oral semaglutide given to lactating mother. Discontinue oral semaglutide at least 2-month before a planned pregnancy. |
CME INDIA Tail Piece
- The recently licensed weight-loss drug semaglutide 2.4 mg/week (Wegovy, Novo Nordisk) “is likely to usher in a new era in the medical treatment of obesity,” Lee M. Kaplan, MD, PhD.
- U.S. Food and Drug Administration approved Wegovy (semaglutide) injection (2.4 mg once weekly) for chronic weight management in adults with obesity or overweight with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol), for use in addition to a reduced calorie diet and increased physical activity (Dated June 4, 2021).
At ADA 2022
- W. Timothy Garvey discussed the results of a study leveraging data from STEP 1 and STEP 4 to determine the reduction in 10-year risk of type 2 diabetes seen with use of semaglutide 2.4 mg vs placebo therapy.
- Use of semaglutide 2.4 mg could reduce the 10-year risk of progression to type 2 diabetes by 60%.
- Having received approval for the treatment of obesity in June 2021, semaglutide 2.4 mg ushered in a new era of weight loss therapies with the FDA’s recognition of the benefit shown in the STEP trials.
References:
- Kane MP, Triplitt CL, Solis-Herrera CD. Management of type 2 diabetes with oral semaglutide: Practical guidance for pharmacists [published correction appears in Am J Health Syst Pharm. 2022 Mar 7;79(6):512-513]. Am J Health Syst Pharm. 2021;78(7):556-567. doi:10.1093/ajhp/zxaa413
- Geometric mean semaglutide concentration–time profiles during a 24-hour dosing interval after the 10th dose. Subjects in the group with upper GI disease had either chronic gastritis, GERD, or both diseases. Meier J et al. 1013–P. ADA 79th Scientific Sessions. June 09, 2019.; Dahl K. et al. Abstract #50. OP 09. EASD 55th
- Singh, Awadhesh & Singh, Ritu. (2022). Oral semaglutide in type 2 diabetes mellitus: Comprehensive review, critical appraisal and clinical consideration of its use in India. Diabetes and Metabolic Syndrome Clinical Research and Reviews. 10.1016/j.dsx.2022.102436.
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Oral Semaglutide helps in weight loss besides glycemic control. The benefits occur at mild GI disturbance. Patients feel happy for the benefits but bothered about the cost.