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Semaglutide

Classification: A

Drug products: Ozempic, Rybelsus

ATC code: A10BJ06

Substances: semaglutide

Summary

Women seem to have a somewhat larger weight drop compared to men. Otherwise, no clinically relevant sex differences have been described. A post-hoc analysis of a randomized trial indicates higher risk of gastrointestinal adverse events in women.

Additional information

Pharmacokinetics and dosing

Both men and women have been included in published pharmacokinetic studies, but results have not been presented separately. The pharmaceutical company does not recommend different doses according to patient’s sex to be necessary [6].

Effects

A post-hoc analysis of data from four trials in the SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) programme (n=1552, around 50% women) found the effect on HbA1C to be similar in men and women. However, women had a greater weight loss than men (-7.0% vs. -4.5% compared to baseline) [7].

Adverse effects

The ACCORD study (Action to Control Cardiovascular Risk in Diabetes) was a randomized, controlled trial designed to test the effect of intensive glucose control compared with standard control on cardiovascular outcomes in patients with type 2 diabetes. The study showed that women had a higher risk of hypoglycemia than men regardless of treatment in general [1].Analyses of other insulins have shown a higher risk for women to have hypoglycemic events [8-12].

In a post-hoc analysis of the SUSTAIN 6 trial including patients with type 2 diabetes and high cardiovascular risk who received semaglutide or placebo once a week (2002 men, 1295 women), gastrointestinal adverse events in all treatment groups were more common among women than men (55.6 vs 48.5% for semaglutide and 37.7 vs 32.0% for placebo), but rates of premature treatment discontinuation were similar for men and women (12.5 and 13.9%, respectively) [13].

Reproductive health issues

Semaglutide can increase the exposure for levonorgestrel at steady state but this is not observed for ethinylestradiol [6]. Semaglutide is contraindicated for use during pregnancy. Semaglutide should be discontinued at least two months before a planned pregnancy due to the long half-life [6]. 

Regarding teratogenic aspects, please consult the Janusmed Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

Two observational studies from the 1990’s (43 men, 374 women) reported intentional insulin omission among 1/3 of women to control their weight [2,3].

In a retrospective study in 124 women, peri-menstrual changes in self-reported glucose concentrations were found in 61%. Use of oral contraceptives did not diminish variability in blood glucose [4]. In another study based on questionnaires (406 women) 67% of the participants reported changes in blood glucose levels or glycosuria pre-menstrually and 70% during the menstrual phase. Those with more cravings had larger elevations in blood glucose levels suggesting that giving in to cravings might cause the changes [5].

Updated: 2020-04-03

Date of litterature search: 2020-02-01

References

  1. Miller ME, Bonds DE, Gerstein HC, Seaquist ER, Bergenstal RM, Calles-Escandon J et al. The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study. BMJ. 2010;340:b5444. PubMed
  2. Polonsky WH, Anderson BJ, Lohrer PA, Aponte JE, Jacobson AM, Cole CF. Insulin omission in women with IDDM. Diabetes Care. 1994;17:1178-85. PubMed
  3. Bryden KS, Neil A, Mayou RA, Peveler RC, Fairburn CG, Dunger DB. Eating habits, body weight, and insulin misuse A longitudinal study of teenagers and young adults with type 1 diabetes. Diabetes Care. 1999;22:1956-60. PubMed
  4. Lunt H, Brown LJ. Self-reported changes in capillary glucose and insulin requirements during the menstrual cycle. Diabet Med. 1996;13:525-30. PubMed
  5. Cawood EH, Bancroft J, Steel JM. Perimenstrual symptoms in women with diabetes mellitus and the relationship to diabetic control. Diabet Med. 1993;10:444-8. PubMed
  6. Ozempic (semaglutide). Summary of Product Characteristics. European Medicines Agency (EMA) [updated 2019-02-20, cited 2020-02-01].
  7. Petri KCC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes. Diabetes Obes Metab. 2018;20(9):2238-2245. PubMed
  8. Seufert J, Brath H, Pscherer S, Borck A, Bramlage P, Siegmund T. Composite efficacy parameters and predictors of hypoglycaemia in basal-plus insulin therapy--a combined analysis of 713 type 2 diabetic patients. Diabetes Obes Metab. 2014;16:248-54. PubMed
  9. Kautzky-Willer A, Kosi L, Lin J, Mihaljevic R. Gender-based differences in glycaemic control and hypoglycaemia prevalence in patients with type 2 diabetes: results from patient-level pooled data of six randomized controlled trials. Diabetes Obes Metab. 2015;17:533-40. PubMed
  10. McGill JB, Vlajnic A, Knutsen PG, Recklein C, Rimler M, Fisher SJ. Effect of gender on treatment outcomes in type 2 diabetes mellitus. Diabetes Res Clin Pract. 2013;102:167-74. PubMed
  11. Owens DR, Bolli GB, Charbonnel B, Haak T, Landgraf W, Porcellati F et al. Effects of age, gender, and body mass index on efficacy and hypoglycaemia outcomes across treat-to-target trials with insulin glargine 100 U/mL added to oral antidiabetes agents in type 2 diabetes. Diabetes Obes Metab. 2017;19:1546-1554. PubMed
  12. Vlckova V, Cornelius V, Kasliwal R, Wilton L, Shakir SA. Hypoglycaemia with oral antidiabetic drugs: results from prescription-event monitoring cohorts of rosiglitazone, pioglitazone, nateglinide and repaglinide. Drug Saf. 2009;32(5):409-18. PubMed
  13. Leiter LA, Bain SC, Hramiak I, Jódar E, Madsbad S, Gondolf T et al. Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial. Cardiovasc Diabetol. 2019;18(1):73. PubMed
  14. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk

Authors: Emelie Elfving, Linnéa Karlsson Lind

Reviewed by: Mia von Euler, Carl-Olav Stiller

Approved by: Karin Schenck-Gustafsson