12/30/2024

Janusmed kön och genus

Janusmed kön och genus – Actos

Janusmed kön och genus är ett kunskapsstöd som tillhandahåller information om köns- och genusaspekter på läkemedelsbehandling. Kunskapsstödet är avsedd främst för hälso- och sjukvårdspersonal. Texterna är generella och ska inte ses som behandlingsriktlinjer. Det är alltid behandlande läkare som ansvarar för patientens medicinering.

För att komma till startsidan för Janusmed kön och genus och för att göra sökningar klicka här.

Tillbaka till index
C C
C C

Pioglitazon

Pioglitazon

Klass : C

Produkter

Actos, Competact, Pioglitazon Orion, Pioglitazone Accord, Pioglitazone......

Actos, Competact, Pioglitazon Orion, Pioglitazone Accord, Pioglitazone Actavis, Pioglitazone Teva Pharma
ATC-koder

A10BD05, A10BG03

A10BD05, A10BG03
Substanser

pioglitazon, pioglitazonhydroklorid

pioglitazon, pioglitazonhydroklorid
Sammanfattning

Hos både kvinnor och män med diabetes som behandlats med pioglitazon i kombination med insulin är risken att dö lägre jämfört med patienter som endast insulinbehandlats. Vissa studier har visat en ökad frakturrisk framförallt hos kvinnor men även hos män behandlade med pioglitazon. Män som behandlas med pioglitazon verkar ha en ökad risk för att utveckla blåscancer.

Hos både kvinnor och män med diabetes som behandlats med pioglitazon i kombination med insulin är risken att dö lägre jämfört med patienter som endast insulinbehandlats. Vissa studier har visat en ökad frakturrisk framförallt hos kvinnor men även hos män behandlade med pioglitazon. Män som behandlas med pioglitazon verkar ha en ökad risk för att utveckla blåscancer.
Background

Studies indicate that men in the early middle age have a higher prevalence of type 2 diabetes mellitus compared with women in the same age group [1]. In Sweden, the age-standardized prevalence of pharmacologically and non-pharmacologically treated diabetes was 56% for men and 39% for women in 2012 [2].
According to the original manufacturer, the mean Cmax and AUC values of pioglitazone is increased 20-60% in women compared to men. HbA1c decreases from baseline were generally greater for women than for men [3,4]. However, other studies (one study 61 men, 63 women, the other 18 men, 19 women) report only small or non-significant sex differences in Cmax and AUC [5, 6].
Some studies report sex differences in pioglitazone pharmacokinetics [3, 5], and the dose should be individualized for each patient. However, no dose adjustment is necessary only based on a patient’s sex. High pioglitazone doses are associated with greater risk of fracture in women aged 50 years and older [7].

Effects
A meta-analysis examining factors associated with reduction in HbA1c from rosiglitazone and pioglitazon......

Studies indicate that men in the early middle age have a higher prevalence of type 2 diabetes mellitus compared with women in the same age group [1]. In Sweden, the age-standardized prevalence of pharmacologically and non-pharmacologically treated diabetes was 56% for men and 39% for women in 2012 [2]. According to the original manufacturer, the mean Cmax and AUC values of pioglitazone is increased 20-60% in women compared to men. HbA1c decreases from baseline were generally greater for women than for men [3,4]. However, other studies (one study 61 men, 63 women, the other 18 men, 19 women) report only small or non-significant sex differences in Cmax and AUC [5, 6]. Some studies report sex differences in pioglitazone pharmacokinetics [3, 5], and the dose should be individualized for each patient. However, no dose adjustment is necessary only based on a patient’s sex. High pioglitazone doses are associated with greater risk of fracture in women aged 50 years and older [7]. # Effects A meta-analysis examining factors associated with reduction in HbA1c from rosiglitazone and pioglitazone, found no impact of sex on the effect size of glitazone therapy on HbA1c [8]. Only pioglitazone is available in Sweden. A small study in Japanese patients (22 men, 26 women) with type 2 diabetes, showed that pioglitazone is likely to show favorable effects on blood glucose control especially in women with higher fasting plasma glucose levels. More women were in the responder group (18 women vs. 4 men). The responders were those showing >1% of reduction in HbA1c after 12 weeks of treatment with pioglitazone 15 mg/day [9]. The risks of all-cause mortality and major cardiovascular events between pioglitazone users and non-users receiving insulin therapy were assessed in a retrospective population-based cohort study in Taiwan (2712 men, 2446 women). The risk of all-cause mortality was lower in pioglitazone users in both men (aHR 0.47, 95% CI; 0.35–0.62) and women (aHR 0.47, 95% CI;0.34–0.65) compared to non-users [10]. # Adverse events **Fracture risk with glitazones in general** Glitazones (pioglitazone, rosiglitazone, troglitazone) have been associated with increased fracture risk. However, results from studies have been inconsistent [11]. Some studies have reported an increased risk only in women (odds ratios varying 1.56-2.23) [7, 12-14], while other studies have reported similar risk in fracture in men and women [15-18]. However, the clinical significance is unclear, clinical trials are relatively small and men have a lower baseline risk of fracture than women [9]. One systematic review of 5 randomized controlled trials (7001 men, 4400 women) reported an increased risk of fractures among women (odds ratio 2.23) but not among men (odds ratio 1.00) treated with pioglitazone or rosiglitazone [17]. One study (48074 men, 36266 women) found that pioglitazone treatment was more strongly associated with fractures than rosiglitazone, in both men and women [18]. Only pioglitazone is available in Sweden. **Fracture risk with pioglitazone** When looking at pioglitazone treatment alone in a meta-analysis (n=3172 patients), neither an increased incidence of fractures (OR=1.18, 95%CI: 0.82 to 1.71) nor an association between fractures and patient’s sex was found [19]. The risk of bone fractures from pioglitazone treatment was investigated in study with safety data from a randomized controlled trial (the Insulin Resistance Intervention after Stroke, IRIS, trial) in nondiabetic patients after an ischemic stroke or TIA (2538 men, 1338 women). The risk of any fracture in the pioglitazone group compared with placebo was increased in men but not in women (HR for men 1.83; 95%CI 1.36-2.48, HR for women 1.32; 95%CI 0.98-1.78) [20]. **Bladder cancer** A meta-analysis (in total 2 321 085 patients) reports an increased incidence of bladder cancer after pioglitazone therapy in men. The mechanisms by which the exposure to pioglitazone causes bladder cancer remains incompletely understood [21]. Pioglitazone-induced adverse drug reactions (ADRs) including bladder cancer were assessed in 19 904 pioglitazone-related individual case safety reports (PG-ICSRs) from the Vigilyze pharmacovigilance database system. Worldwide, the distribution of overall PG-ICSRs was higher in men (37%) compared to women (30%). Unfortunately, in 34% of the PG-ICSRs, the patient’s sex was not reported. The percentage of PG-ICSRs associated with bladder cancer was fivefold higher in men (27%) than women (6%). In as high as 67% of these PG-ICSRs, the patient’s sex was not reported [22]. In a study with data from the National Health Insurance program in Taiwan, the incidence of gout was investigated in diabetics (30 100 pioglitazone users and 90 300 non-pioglitazone users with 52.4% women in each population). The incidence of gout was lower in both men  and women (aHR 0.80 and 0.83, respectively) using pioglitazone than in non-pioglitazone users [23]. In a retrospective cohort study in patients with diabetes in Taiwan, pioglitazone use was not associated with Parkinson disease  incidence in users (3696 men, 4210 women) compared to non-users (3696 men, 4210 women) [24]. # Reproductive health issues Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan). # Other information The influence of pioglitazone on body composition in older non-diabetic overweight/obese men and women during weight loss  (48 men, 40 women, 65-79 years) showed that pioglitazone reduced abdominal visceral fat in men but not in women. Loss of subcutaneous fat in thigh was attenuated in women taking pioglitazone. This sex differences can be explained by differences in adipose tissue loss from the visceral and subcutaneous compartments during weight-loss trials [25]. Pioglitazone’s potential effects on basal cortisol levels and the growth hormone-insulin-like growth factor (GH-IGF) axis, was investigated in an interventional study in type 2 diabetes patients with secondary drug failure (28 men, 20 women). IGF-I and adiponectin increased significantly in both men and women, while triglycerides decreased significantly in women only. The authors discuss that increased IGF-I may contribute to improved insulin sensitivity after treatment [26]. In a RCT with patients newly diagnosed with diabetes, the effects of metformin (22 men, 19 women) and pioglitazone (19 men, 31 women) on omentin and leptin concentrations were investigated. After three months, metformin decreased both omentin and leptin concentrations in women, and leptin concentrations only in men. On the other hand, pioglitazone reduced both adipokines only in women, but not men [27].
Försäljning på recept

Fler män än kvinnor hämtade ut tabletter innehållande pioglitazon (ATC-kod A10BG03) på recept i Sverige år 2020, totalt 3 303 män och 1 880 kvinnor. Det motsvarar 0,6 respektive 0,4 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70-79 år hos båda könen. I genomsnitt var tabletter innehållande pioglitazon 1,6 gånger vanligare hos män [28]. Något fler män än kvinnor hämtade ut tabletter innehållande kombination av metformin och pioglitazon (ATC-kod A10BD05) på recept i Sverige år 2020, totalt 46 män och 18 kvinnor [28].
Referenser
  1. Gale EA, Gillespie KM. Diabetes and gender. Diabetologia. 2001;44(1):3-15.
  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.
  3. DailyMed Actos (pioglitazone). DailyMed [www]. US National Library of Medicine. [updated 2021-01-13, cited 2021-07-15].
  4. Pioglitazone pharmacokinetics. Drugs.com [www]. [updated 2021-06-21, cited 2021-07-15].
  5. Karim A, Slater M, Bradford D, Schwartz L, Zhao Z, Cao C et al. Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and metformin Effect of body weight, gender, and race on systemic exposures of each drug. J Clin Pharmacol. 2007;47:37-47.
  6. Karim A, Zhao Z, Slater M, Bradford D, Schuster J, Laurent A. Replicate study design in bioequivalency assessment, pros and cons: bioavailabilities of the antidiabetic drugs pioglitazone and glimepiride present in a fixed-dose combination formulation. J Clin Pharmacol. 2007;47:806-16.
  7. Bilik D, McEwen LN, Brown MB, Pomeroy NE, Kim C, Asao K et al. Thiazolidinediones and fractures: evidence from translating research into action for diabetes. J Clin Endocrinol Metab. 2010;95:4560-5.
  8. Phatak HM, Yin DD. Factors associated with the effect-size of thiazolidinedione (TZD) therapy on HbA(1c): a meta-analysis of published randomized clinical trials. Curr Med Res Opin. 2006;22:2267-78.
  9. Tajiri Y, Takei R, Mimura K, Umeda F. Indicators for the efficacy of pioglitazone before and during treatment in Japanese patients with type 2 diabetes. Diabetes Technol Ther. 2007;9:429-37.
  10. Yen FS, Wang HC, Pan CW, Wei JC, Hsu CC, Hwu CM. Pioglitazone Exposure Reduced the Risk of All-Cause Mortality in Insulin-Treated Patients with Type 2 Diabetes Mellitus. J Clin Endocrinol Metab. 2020;105(2).
  11. Lecka-Czernik B. Bone loss in diabetes: use of antidiabetic thiazolidinediones and secondary osteoporosis. Curr Osteoporos Rep. 2010;8:178-84.
  12. Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ. 2009;180:32-9.
  13. Aubert RE, Herrera V, Chen W, Haffner SM, Pendergrass M. Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes. Diabetes Obes Metab. 2010;12:716-21.
  14. Habib ZA, Havstad SL, Wells K, Divine G, Pladevall M, Williams LK. Thiazolidinedione use and the longitudinal risk of fractures in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2010;95:592-600.
  15. Meier C, Kraenzlin ME, Bodmer M, Jick SS, Jick H, Meier CR. Use of thiazolidinediones and fracture risk. Arch Intern Med. 2008;168:820-5.
  16. Douglas IJ, Evans SJ, Pocock S, Smeeth L. The risk of fractures associated with thiazolidinediones: a self-controlled case-series study. PLoS Med. 2009;6:e1000154.
  17. Jonas D, Van Scoyoc E, Gerrald K, Wines R, Amick H, Triplette M, Runge T. Drug Class Review: Newer Diabetes Medications, TZDs, and Combinations: Final Original Report . Oregon Health & Science University.
  18. Dormuth CR, Carney G, Carleton B, Bassett K, Wright JM. Thiazolidinediones and fractures in men and women. Arch Intern Med. 2009;169:1395-402.
  19. Pavlova V, Filipova E, Uzunova K, Kalinov K, Vekov T. Pioglitazone Therapy and Fractures: Systematic Review and Meta- Analysis. Endocr Metab Immune Disord Drug Targets. 2018;18(5):502-507.
  20. Viscoli CM, Inzucchi SE, Young LH, Insogna KL, Conwit R, Furie KL et al. Pioglitazone and Risk for Bone Fracture: Safety Data From a Randomized Clinical Trial. J Clin Endocrinol Metab. 2017;102(3):914-922.
  21. He S, Tang YH, Zhao G, Yang X, Wang D, Zhang Y. Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis. Tumour Biol. 2014;35:2095-102.
  22. Bhushan S, Ray RS, Prakash J, Singh GN. Global Versus Indian Perspective of Pioglitazone-induced Adverse Drug Reactions Including Bladder Cancer: A Comparative Retrospective Pharmacovigilance Analysis. Clin Ther. 2019;41(11):2252-2262.
  23. Niu SW, Chang KT, Lin HY, Kuo IC, Chang YH, Chen YH, Hung CC, Chiu YW, Hwang SJ. Decreased incidence of gout in diabetic patients using pioglitazone. Rheumatology (Oxford). 2018;57(1):92-99.
  24. Wu HF, Kao LT, Shih JH, Kao HH, Chou YC, Li IH et al. Pioglitazone use and Parkinson's disease: a retrospective cohort study in Taiwan. BMJ Open. 2018;8(8):e023302.
  25. Shea MK, Nicklas BJ, Marsh AP, Houston DK, Miller GD, Isom S et al. The effect of pioglitazone and resistance training on body composition in older men and women undergoing hypocaloric weight loss. Obesity (Silver Spring). 2011;19:1636-46.
  26. Arnetz L, Dorkhan M, Alvarsson M, Brismar K, Ekberg NR. Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes. Acta Diabetol. 2014;51(2):185-92.
  27. Esteghamati A, Noshad S, Rabizadeh S, Ghavami M, Zandieh A, Nakhjavani M. Comparative effects of metformin and pioglitazone on omentin and leptin concentrations in patients with newly diagnosed diabetes: a randomized clinical trial. Regul Pept. 2013;182:1-6.
  28. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2020 [cited 2021-03-10.]
Uppdaterat

Litteratursökningsdatum: 7/15/2021

Litteratursökningsdatum: 7/15/2021
Fasstexter