Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Vildagliptin

Klassificering: C

Preparat: Eucreas®, Galvus®

ATC kod: A10BD08, A10BH02

Substanser: vildagliptin

Sammanfattning

Effekten av vildagliptin på enzymet dipeptidylpeptidas-4 (DDP-4) är likvärdig hos kvinnor och män. En subgruppsanalys med tillägg av vildagliptin till metformin hos kvinnor över 45 år med diabetes visade att HbA1c-målet uppnåddes mindre sällan utan viktuppgång jämfört med kvinnor yngre än 45 år.

En trefaldigt ökad risk för bullös pemfigoid hos diabetespatienter som behandlas med dipeptidyl peptidas-4 (DPP-4) -hämmare på gruppnivå har noterats och denna risk har setts vara oberoende av metforminbehandling samt högre hos män.

Män med anamnes på tidigare perifert ödem som förskrivs vildagliptin har en ökad risk att få perifert ödem jämfört kvinnor.

Additional information

For type 1 diabetes mellitus when diagnosed under the age of 15, the prevalence between boys and girls is similar. In adult populations of patients with both type 1 and 2 diabetes, the differences between the sexes in prevalence seem to vary depending on several factors such as incidence of disease, age groups and ethnicities studied.  Studies indicate that men in the early middle age display a higher prevalence of type 2 diabetes mellitus compared with women in the same age group [1]. In a nationwide population-based pharmaco-epidemiological study in Sweden, the total age-standardized prevalence of pharmacologically and non-pharmacologically treated diabetes (2012) was 56% for men and 39% for women [2].

Pharmacokinetics and dosing

In an open, parallel-group, clinical study, young and elderly healthy volunteers (20 men, 20 women) received a single dose of 100 mg vildagliptin. No clinically relevant differences in pharmacokinetic parameters were observed between men and women [3-5]. No dose adjustment based on patient’s sex is necessary [6].

Effects

Vildagliptin inhibits the enzyme dipeptidyl-peptidase-4 (DDP-4), which increases endogenous levels of incretin hormones, resulting in improved glucose-dependent insulin secretion. Inhibition of DDP-4 by vildagliptin is not affected by patient’s sex [3, 4]. No clinically relevant outcome studies have been found.

A post-hoc analysis [7] of the EDGE study [8] assessed inter-regional differences in baseline characteristics and response to treatment intensification with dual oral antidiabetic drugs in patients with type 2 diabetes (23,990 men, 19,801 women) [7]. Vildagliptin add-on therapy to metformin allowed more patients to achieve glycemic target HbA1c <7% without hypoglycemia or weight gain ⩾ 3% at 12 months (the secondary end point, SEP), across regions. Subgroup analysis showed that women aged ⩾45 years less often attained glycemic target without significant weight gain ⩾5% compared with women aged <45 years (OR 0.876) [7]. Study results for women compared to men were not presented.

Adverse effects

A large meta-analysis (7458 men, 6112 women) reported that vildagliptin was not associated with an increased risk of cardiovascular or cerebrovascular events, neither in men nor in women, relative to comparative drugs [4].

Using Korean insurance claims data, the potential association between the use of DPP-4 inhibitors and increased risk of developing bullous pemphigoid was assessed (684 men, 656 women). The use of DPP-4 inhibitors was associated with a significant increase in the risk of developing bullous pemphigoid (OR 1.58) with vildagliptin having the highest OR (1.81). Subgroup analyses showed an association in men (OR 1.91) and with vildagliptin being the most high-risk DPP-4 inhibitor (OR 2.70) [9].

A retrospective case-control study from Israel (190 men, 220 women) showed a 3-fold increased risk for bullous pemphigoid in patients with diabetes treated with DPP-4 inhibitors (adjusted OR for vildagliptin 10.7 and for linagliptin 6.7). The association of DPP-4 inhibitor use with bullous pemphigoid was independent of the use of metformin and was stronger among men (OR 4.46; 95% CI, 2.11-9.40) than women (OR 1.88; 95% CI, 1.73-18.01) [10]. 

Another retrospective case-control study from France and Switzerland (90 men, 93 women) compared patients with diabetes and bullous pemphigoid with age- and sex-matched control patients with diabetes. The study showed that DPP-4 inhibitors were associated with an increased risk of developing bullous pemphigoid (adjusted OR 2.64; 95% CI 1.19-5.85), with vildagliptin showing the highest risk (adjusted OR 3.57; 95% CI 1.07-11.84). Sex-stratified analysis indicated that the effect of a DPP-4 inhibitor on bullous pemphigoid onset was higher in men (adjusted OR 4.36; 95% CI, 1.38-13.83) than women (adjusted OR 1.64; 95% CI 0.53-5.11) [11].

A per-protocol supplementary analysis of a vildagliptin post-marketing study (2692 men, 2132 women) compared the risk of peripheral edema between vildagliptin monotherapy and combination therapy with sulfonylurea. Men of average age (62 years) prescribed vildagliptin are estimated to have approximately 13 times higher risk of peripheral edema if they have a prior history of the condition (HR 12.84, 95 %CI 4.96–33.23), whilst no such relationship is observed for women of average age (HR 1.44, 95 %CI 0.32–6.40) [12].

The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 (SGLT2) inhibitors versus DPP-4 inhibitors was evaluated in an observational study from Taiwan. The subgroup analysis showed a lower risk of incident atrial fibrillation for SGLT2 inhibitors (9091 men, 6515 women) versus DPP-4 inhibitors (6911 men, 5472 women) in women compared to men with type 2 diabetes (HR men 0.51, HR women 0.70, p interaction =0.10) [13].

Reproductive health issues

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

Försäljning på recept

Något fler män än kvinnor hämtade ut tabletter innehållande vildagliptin (ATC-kod A10BH02) på recept i Sverige år 2020, totalt 210 män och 150 kvinnor [14].

Något fler män än kvinnor hämtade ut tabletter innehållande kombination av metformin och vildagliptin (ATC-kod A10BD08) på recept i Sverige år 2020, totalt 108 män och 40 kvinnor [14].

Uppdaterat: 2021-09-27

Litteratursökningsdatum: 2021-05-26

Referenser

  1. Gale EA, Gillespie KM. Diabetes and gender. Diabetologia. 2001;44(1):3-15. PubMed
  2. Jansson SP, Fall K, Brus O, Magnuson A, Wändell P, Östgren CJ et al. Prevalence and incidence of diabetes mellitus: a nationwide population-based pharmaco-epidemiological study in Sweden. Diabet Med. 2015;32(10):1319-28. PubMed
  3. GALVUS (vildagliptin). Summary of Product Characteristics. European Medicines Agency (EMA); [updated 2020-03-11, cited 2021-05-26]
  4. He YL, Sabo R, Campestrini J, Wang Y, Riviere GJ, Nielsen JC et al. The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteers. Br J Clin Pharmacol. 2008;65:338-46. PubMed
  5. He YL, Sadler BM, Sabo R, Balez S, Wang Y, Campestrini J et al. The absolute oral bioavailability and population-based pharmacokinetic modelling of a novel dipeptidylpeptidase-IV inhibitor, vildagliptin, in healthy volunteers. Clin Pharmacokinet. 2007;46:787-802. PubMed
  6. Schweizer A, Dejager S, Foley JE, Couturier A, Ligueros-Saylan M, Kothny W. Assessing the cardio-cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events from a large Phase III type 2 diabetes population. Diabetes Obes Metab. 2010;12:485-94. PubMed
  7. Brath H, Paldánius PM, Bader G, Kolaczynski WM, Nilsson PM. Differences in glycemic control across world regions: a post-hoc analysis in patients with type 2 diabetes mellitus on dual antidiabetes drug therapy. Nutr Diabetes. 2016;6(7):217. länk
  8. Mathieu C, Barnett AH, Brath H, Conget I, de Castro JJ, Göke R, Márquez Rodriguez E, Nilsson PM, Pagkalos E, Penfornis A, Schaper NC, Wangnoo SK, Kothny W, Bader G. Effectiveness and tolerability of second-line therapy with vildagliptin vs other oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE). Int J Clin Pract. 2013;67(10):947-56. PubMed
  9. Lee MP, Desai RJ, Jin Y, Brill G, Ogdie A, Kim SC. Association of Dipeptidyl Peptidase 4 Inhibitor Use With Risk of Bullous Pemphigoid in Patients With Diabetes. JAMA Dermatol. 2019;155(2):172-177. PubMed
  10. Kridin K, Bergman R. Association of Bullous Pemphigoid With Dipeptidyl-Peptidase 4 Inhibitors in Patients With Diabetes: Estimating the Risk of the New Agents and Characterizing the Patients. JAMA Dermatol. 2018;154(10):1152-1158. PubMed
  11. Benzaquen M, Borradori L, Berbis P, Cazzaniga S, Valero R, Richard MA et al. Dipeptidyl peptidase IV inhibitors, a risk factor for bullous pemphigoid: Retrospective multicenter case-control study from France and Switzerland. J Am Acad Dermatol. 2018;78(6):1090-1096. PubMed
  12. Layton D, Coughtrie AL, Qayum N, Shakir SA. Pattern of Onset and Risk Factors for Peripheral Oedema During Vildagliptin Use: Analysis from the Vildagliptin Prescription-Event Monitoring Study in England. Drug Saf. 2016;11(11):1093-1104. länk
  13. Ling AW, Chan CC, Chen SW, Kao YW, Huang CY, Chan YH, Chu PH. The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors. Cardiovasc Diabetol. 2020;19(1):188. länk
  14. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2020 [cited 2021-03-10.] länk

Författare: Diana Rydberg, Linnéa Karlsson Lind

Faktagranskat av: Alan Fotoohi

Godkänt av: Karin Schenck-Gustafsson