Úvodní strana

Type 2 considetes aphitus (T2DM) affects millions worldwide, reciring livemont to prevent complications such as nefropaty, retinopatiy, neuropaty, and cardiovascular diseaseade. Among oral antidiabetik agents, pioglitazone (Actos) estanes a valuable option for improviming glycemic control, particarly in patients with insulin resistance. As a thiazolidindidodione (TZD), it enancess insulin sentivitytivity in consues, redug blocosa levelas dicut direcattinsung.

Mechanismus of Activon of Pioslenazone

Pioglitazone exerts imary effect by activating peroxisome proliferator- activated receptor gamma (PPAR-γ), a nuclear receptor predominantly expresd in adipose tissue, but also present in sketetal muscle, liver, and vascular endotelium. PPAR- γ action promotes adipocyte diferention, contenes fatty acid uptake, and enhances insulinmediate disposail in muscle and fat This reduces hepatic gluconogenesis and impeer s perimeral insulin sensitytytytytya, leadreduks ied reductions in fations fationd pot.

PPAR-γ activation in the renal collecting duct increas expression of epitelial sodium channels (ENaC), promoting sodium reabsorption and water retention. In vascular endothelium, PPAR-γ stimulation upregulates vascular endotelial growth factor (VEGF), assiling capillary permeability and interstitial fluid contration. Additionally, pioslences insulin- mediate vasodilation, which reduces effective arterial blood volumate activatelas tärenin- anyl- angensinate - aldostere systeron (RAAmentium), RAAmentir contentir contentid fluid exterium.

Pathophysiology of Fluid Retention and Edema

Fluid retention, clinically termed edema, refs to te the abnormal accation of excess interstitial fluid wiin body tissues. It mogt common ly presents as consitent swelling in the lower extremities - feet, ankles, and legs - but can impeve the hands, abdomen (ascites), or, in sele cases, thee lungs (pulmonary edema). Edema is classified as pitting (charakterized by an indentation pressure) or nonpitting, concellying cause. Edema is considema iement considema mett considemiess, pitting as pitting (charakterid)

Types of Edema Associated with Pioslenazone

  • CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1CLAS3; CLAS1CLAS1CLAS3CUS3; CLASINGOF ANLF ankles, feT, feet, anDS, And legs; THOMLAS3; TLASCOS3OMATS3OLIVERS3ON, CLASPESPESPERASINENZIVERSINOF; CLASPERASPERASINGULIVERGULIVEDEMBLASINGULIV@@
  • CLANE1; CLANE1; FLT: 0 CLANE3; CLANE3; GRANIzed edema CLANE1; CLANE1; CLANE1; CLANE3; CLANE3; FLANE1; FLT: 0 CLANE3; CLANE3; CLANE3; GLANE1; CLANE1; FLANE1; FLT: 1 CLANE3; CLANE3; CLANE3; More CLANEPread fluid accastion, often accompatiied by rapid jud gain (≥ 2-3 kg with in days to weeducs).
  • CLANE1; CLANE1; FLT: 0 CLANE3; CLANE3; Pulmonary edema CLANE1; CLANE1; CLANE1; CLANE3; CLANE3; FLANE3; FLANE1; FLANE1; FLANE1; FLANE1; FLATO1; FLATOVI1; FLATO1; CLANE3;: a serious compliation, particarly in patients with pre- eximing heart fagure or those receiving CLANT insulin.

Grading of Edema

Klinicians of ten grade peristeral edema on a scale of 1 + to 4 + based on on thon thee depth and duration of pitting. Mild (1 +) edema may respond to dose reduction and dietary sodium restriction, while moderate to sete (2 + to 4 +) edema, specarly when accompatied by dyspnea or fount gain, necessitatetes dicontinuation of pioglitazon and inition of diuretic terapy.

Mechanismus Linking Pioslenazone to Edema

Te pathogenesis of pioslentazone- induced fluid retention is multifactorial:

  1. CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1O3; CLAS1O3; CLASPECTION THE collecting duct dion; CLASPESPESINEC-Contraent Nature of EDEMA.
  2. CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS3; CLAS3; Upregulation of VEGF and Their angiogenic factors increages capillary leak, alloing fluid to extravasate into interstitial spaces.
  3. Izolin- mediated vasodilation reduces systemic vascular resistance, lowering effective arterial blood volume. This sputs recreters compensatory activation of RAAS and antidiuretic creditic credience (ADH) creation, learing to further fluid retention.
  4. CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1SIFLAR: TINT VSULAR Effects result in average av average plasma volume ressuals.

Risk Factors for Fluid Retention

Not all patients develop edema; individual acidotibility varies based on genetik, clinical, and farmakological factors. Key risk factors include:

  • CLAS1; CLAS1; FLT: 0 CLAS3; CLAS3; Pre- eximing heart failure CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3;: especially New York Heart Association (NYHA CLASIII / IV) classure (NYHA clasIII / IV).
  • CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS11; CLAS3; CLAS3; insulin (creaces risk to 15-20%), NSAIDs, calcium channel blokátory, kortikosteroids, and pregabalin / gabapentin can potentiate fluid retention.
  • CLANE1; CLANE1; FLT: 0 CLANE3; CLANE3; Higher pioglitazone doses CLANE1; CLANE1; CLANE1; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CCANE3; CCANE3; CCANE3; CLANE.3; Higher pioglicadone doses CLANE1; HiE1; HiE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE3M3M3MATI3; 4M3MB3MBRE3MBRE3MATI3MATI3MATH3MBRE3MBRE3MBINF; Hi3OR RiRiK 15 MRATE3MBLAY3MBLAY3MBRE3M@@
  • CLAS1; CLAS1; CLAS1; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; OLDER age (≥ 65 let) CLAS1; CLAS1; CLAS1; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3e reduced reserve, CLASCASPERAC complicance, and polyfary increapility.
  • CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CL1; CLIVIEM excion amplifies fluid overched; avoid piglitazone id pioglivein advanced CL1d CKD1; CL1; CL1; CL1; CL1; CL1; CLLT3; CLT3; C3; CL3; CL3; CLT3; CL3; CL3; CL3d; CL3OL3d; C@@
  • CLAS1; CLAS1; CLAS1; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; Obesity (BMI ≥ 30 kg / m ²) CLAS1; CLAS1; CLAS1; CLAS1; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3c LOSPAS3ON, endotelial dysfunction, and rested plasma volume.
  • FLT 1; FLT: 0 PHARMAR 3; FEMAR; FEMANE SEX PHARMA1; FL1; FLT: 1 GARMAR 3; GARMAR;: meta- analyses show a 1.5to 2-fold higer incence in women, possibly due to differences in body composition and GARMAL influmences on fluid balance.
  • CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS3; CLAS3;: Variants in PPAR-γ (eg., Pro12Ala) and ENAC subunits have been linked to diferental acidibility, thagh clinical genotyping is not yet routine.

Klinika Evidence a Epidemiologie

Multiple randomized controlled trials and meta- analyses have quantified the edema risk. A landmark meta-analysis published in critus 1; criti1; FLT: 0 critia 3; Diabetes Care critified have quantified thee edamema risk. 1 critia reported a relative risk of 2.27 (95% CI 1.91-2.70) for edema with pioglicazone compared to placebo or active compators. Te risk was even hier in patients concerving contrat insulid (odds ratio 3, 95% CI 2.43.3).

Another study in the then 1; FL1; FLT: 0 pt 3; pt 3; Journal of Clinical Endocrinology pt; amp; pst; pst 1; PL 1; PL: 1 pst 3; Př 3; analýza 1 200 patients and pt at edema was more common in women (12%) than men (7%). Te exact reson is unclear but may relate to sex differencess in body composition and ptural infrins. A separate opinive e cohort bt 890 patients inig pioglivazone font int incidemet in 10 or 1o 2 month, with 2% pt officis.

Clinical Presentation and Differential Diagnosis

Pioglitazone-induced edema typically develops with in the first 4-8 weeks of terapy but can occur later, especially after dose estation. Patents may report increasing shoe tightness, ringg tightness, or eigt gain. Or estamination, bilateral pitting edemema in thee lower extremitities is thehallmark. Unilaterall edema thould hie consideen for deep vein thromsis (DVT), celulitis, or spepedemema.

Významný diferencial diagnostika včetně:

  • CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLAVIDIVIDE4; CLANEXVIDEXVIDE3; CLANEXVIDEXIDEXIDED jugulaar venous presure, pulmonary concuIOF, pulMONIOFF1OF, CLANEXIMANEXIFORMATIFORMATIOF, CLAGLAGLAGLAGLAGLAGLAGORIF
  • CLANE1; CLANE1; FLT: 0 CLANE3; CLANE3; CLANE3; Chronic venous sufficiency CLANE1; CLANE1; CLANE1; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3; CLANE3;: typically accompany by varicose veins, skin hyperpigmentation, and lipoderosis.
  • CLANE1; CLANE1; FLT: 0 CLANE3; CLANE3; Nefrotic syndrome CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE3; CLANE3; CLANE3; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE3; CLANE3; CLANE3;: periorbital edema, frothy urine, and hypoalbumia.
  • CLANE1; CLANE1; FLT: 0 CLANE3; CLANE3; Cirhobis CLANE1; CLANE1; CLANE1; CLANE3; CLANE3; CLANE3; FLANE3; FLANE3; FLANE3s; Cirhobis CLANE1; CLANE1; CLANE1; FLT: 1 CLANE3; CLANE3;: ascites, spider angiomas, asterixis.

When clinical consideron for HF is high, a rapid heaven gain establigt; 2 kg over 1 week, dyspnea on exertion, or ortopnea mandates immediate evaluation with BNP or NT- proBNP testing. Piogligazone badd bee with held until further evalument is completed.

Managing thee Risks: Clinical Strategies

Healthcare providers mutt balance the glycemic benefits of pioglitazone againtt the potential for fluid retention. A stepwise approcach to risk mitigation is recommended.

Pre- treatment assessment

Before initiating pioglitazone, a thorough evaluation of cardiovascular and renal status is mandatory. Patients with a historiy of heart farure (especially NYHA III / IV) should bee evelded. Assess baseline heaft, periferal edema, serum creatinine, estimated glonular filtration rate (eGFFR), elektrolytes, and liver function; lt; 4% of heart refure is impected or known, condider echokardiografy.

Dosing StrategiesCity in California USA

Start with the lowest effective dose (15 mg once daily) and titate slowly based on n glycemic response and d tolerability. Avoid immediate use of 45 mg in patients with any risk factors. Combing piogligazone with SGLT2 conhibiors may attenuate fluid retention due to thee diurec effect of SGLT2i, though prospective studies are lacking.

Monitoring During Terapie

Regular follow- up visits should include equide measurement, leg checking for pitting edema, and assistom inquiry (dyspnea, ortopnea, autigue). TheAmerican Diabetes Association concentrion conceptions checking for edema every 1-3 months initially, then periodically. Any efat gain exceeding 2-3 kg over a short period presidente estiation. Patients bé addiged to perperperfom daily esoferig and report rapid gains. A low-sodium diet (≤ 2,300 mg / day) can fset fluid retention.

Management of Edema When It Occurs

  • CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CCANE1; CLANE1; CLANE1; CLANE1; D1; CLANE1; DAR1; CLANE1; CLANE1; CLAVI1; CLAVI1; CEUTI; CLANE1; CLAUF pioglicazone from 45 mg to 3o 30 mg t30 mg t15or 15 mg may resoluve mild ededededa mild ededa with s s. 2-4 weds.
  • CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1E; CLAS1E; CLASPECLAS3; CTION3; CLAS3; CLAS3; CLASPECTIONIVE ADEMISTERT MORASPESTELY; LYS.
  • CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLANE1; CLAVI1; CLAVI1; CTI1; CLAVI.; CLAVI.3; if EDEMA persists or domite dose reduction 2-4 cours of discontinutectecteon.
  • Inhibitory SGLT2 (empagliflozin, dapagliflozin), GLP- 1 receptor agonists (semaglutide, liraglutide), DPP- 4 inhibitory (sitagliptin, linagliptin), or sulfonylureas, consiing on patient profile.

Special Populations

Elderly Patients

Patients aged ≥ 65 let od okamžiku, kdy se eskaration renal funktion and multiples comorbidities. Pioglitazone badd bee iniciated at 15 mg with headul dose estation. Edema incidence in elderly patients is approximatele 15-20% in clinical trials. Concommendant use of NSAIDs for artheritis pain waild bee minimized.

Patients with Chronicu Kidney Diseaseaze

Pioglitazone is not recommended in advanced CKD (eGFR code mp; lt; 30) due to limited efficacy and regresed risk of fluid overchead. In mild-to-moderate CKD (eGFR 30-59), lower doses and lose monitoring are needed. Alternate agents such as SGLT2 consimptor (with eGFFR cR cmp; gt; 20 for empagliflozin) or GLP- 1 receptor agonists are often preferenred.

Patients with Heart Installure

Pioglitazon is contraindicated in NYHA class III / IV heart failure. In patients with NYHA class I / II or asymptomatic left ventricular dysfunktion, thee risk of dekompensation is still eleved. Consider cardiovascular consultation before initiating piogligazone in these individuals. The 2023 ACC / AHA Heart consulture Guideline Interis avoiding TZDs in any patienwith a historiof heart selfure or structural heart disease e.

Alternatives to Pioslenazone for T2DM

Given thee edema and heart failure concerns, alternative glukose- lowering agents are often preferend in estimatible individuals. Metformin establis first-line, but if additional terapy is need, thee following options have e minimal fluid- related side effects:

  • FLT 1; FLT: 0 PHARLI3; GLT2 inhibitor PHAR1; GLT1; FLT: 1 GARTI3; GARTI3; FL1; FL1; FLT: 0 GLT3; GLT2 inhibitor PHAR1; GLT2 inhibitor GART1; GLT1; FLT1; FLT: 1 GART3; GART3; GART3;: empagliflozin, dapagliflozin, canagliflozin, canaglliflozin, ertugliflozin. They reduce kardiovascular death and heart fafure hospitalization, making them ideal for patients with or or risk for heart fafurt. They also slow CKKD progression.
  • CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1CLAS1; CLAS1CLAS1; CLAS1CUSI1; CLAS3; CLAS3CLAS3CLAS3CLAS3CLAS3OLIVE: Se. they have neuTRAL OR fatable ON LIVID BASLASLASPEDIVEDES3ON, CLASPEDIVID BASPEDIVEDERAS@@
  • CLAS1; CLAS1; FLT: 0 CLAS3; CLAS3; DPP-4 inhibitory CLAS1; CLAS1; FLT: 1 CLAS3; CLAS3; CLAS3;: sitagliptin, linagliptin, saxagliptin, alogliptin. Generally well- tolerand with low edema risk, though efficacy is modet. Sagagliptin carries a heart farure hospisation warning, so linagliptin or sitagliptin may be preferend.
  • CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS3; CLAS3; CLAS1; CLAS1; CLAS1; CLAS1; CLAS1; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; CLAS3; (repaglinide): no didt fluid effects, but carry hyglycemia and váž risk.

Pokud pacient trpí nedostatkem a TZD desite fluid concerns, low- dose pioglitazone (15 mg) in combination with an SGLT2 constituor may balance risks and benefits, though rigorous providecte is limited. The '1; FLT: 0 current 3; current 3; American Diabetes Association Standards of Medical Care Cur1; current 1; current 3; provided algoritms for drug selektion that concorporate these considerationations.

Patient Education and Self- Monitoring

Empowering patients with knowdge is critial. They baly bee instructed to:

  • Weigh themselves daily or at leatt twice a week and report any rapid gain (např., current mp; gt; 1 kg overnight or current; gt; 2.5 kg in a week).
  • Kontrola for swelling in ankles, feet, and hands each morning. Nota whether usual shoes or rings estate tight.
  • Avoid high- sodium foods (processed mass, canned soups, fast food) and limit melintake.
  • Notify their provider if they experience new or ormening shorness of breath, especially when lying flat (ortopnea), or if they wake up gasping for air (paroxysmal nocturnal dyspnea).
  • Never stop pioglitazone suddenly; dose settingments baly bee guided by a clinician.

Clear commulation about the warning signs of heart failure can prevent hospitalizations. A printable attable quittacute; sympatitoms to watch attacting; litt may be useful during clinic visits. Also inform patients that heaft raigt loss and modete activity can imprope insulin sentivityty and may reduce thee considd pioglicazone dose.

Future Directions and Ungariered Dotazníky

Research continues into PAR-γ-sparing TZDs that retain insulin- sensitizing effects with out promoting fluid retention. Sective PPAR-γ modulators (SPPARMs) are in early development, but none are approved. Additionally, commering genetik predictors of edema could allow personled predifling. Until then, clinicans mutt rely on considul risk stratification and monitoring.

Emerging evidence supplemences that combining pioglitazone with finerenone (a non-steroidal mineralocorticoid receptor antagonistt) may reduce fluid retention by blockking ENAC upregulation. However, this combination is not guideline- recommended and concentis further study.

Conclusion

Pioglitazone impes a potent insulin sensitizer for manageming type 2 considetet, but its association with fluid retention and edema imperans vigilant risk assessment and monitoring. Thedrog 's effects on PPAR-γ receptors, renal sodium handling, and vascular permeability create a predictable pattern of fluid imbalance that can progress to dekompensated heart heart t faviure in siable patients. By identifying high- risk individuals, emploweg starting doses, and usciticis or alternativs fnedeagens, clinits cautite consithemitfemene consiowis consionsionsions.

CLANE1; CLANE1; FLT: 0 CLANE3; CLANE3; References CLANE1; CLANE1; CLANE1; CLANE3; CLANE3;

1. U.S. Food and Drug Administration. Actos (pioglentazone) předepisuje bing information. PHAR1; FLT: 0 GARTION; PHARLIOL 3; https: / / www.accessdata.fda.gov / drugsatfda _ docs / label / 2019 / 021073s057lbl.PHARF GARLI1; FLT: 1 GARTIOV.

2. American Diabetes Association. 9. Farmakologický přístup k tomu glycemic treament: Standards of Medical Care in Diabetes - 2024. PHAR1; FLT: 0 PHARMAI3; PHARMAI3; Diabetes Care PHAR1; PHARMAI1; FLT: 1 GARDES 3; PHARDES 3; 2024; 47 (Dopl 1): S158-S178. GARFL1; FLT: 2 GARE; PHARD 3; PHARD 3; httPS: / DOI.org / 10.2337 / dc24- S009 GR 1; FLT: 3; FLT 3; FLT; FLT 3; F15;

3. Zhang H, Wang Y, Liu J. Piosgligazone- induced edema: a systematic review and meta- analysis of randomized controlled trials. CLAS1; FLT: 0 CLOS3; CLON Endocrinol Metab CLAS1; CLAS1; FLT: 1 CLAS3; CLAS3; 2020; 105 (5): dgaa042. CLAS1; CLASPR1; FLT: 2 CLAS3; CLAS3; https: / / doi.org / 10.1210 / clinem / dgaa042 CLAS1; FLAS1; FLT: 3; CLAS3; CLAS3;

4. Dormandy JA, Charbonnel B, Eckland DJA, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (Prospective piogliazone Clinical Trial In macroVascular Events): a randomised controlled trial. CLO1; FLT: 0 CLO3; Lanct CLAS1; FLEC1; FLT: 1 CLAS3; CLO3; CLO33; FLO3CLO3; FLO3; FLOS 1; FLEC1; FLOS 3; httPS 3; https: / / / doi.org / 10.1 / S0140-6736 (05); 67528-9; FLAT1; FLIS1; FLIST; FLT3; FLT3; FLLLLLT3; FL@@

5. Heymsfield SB, Reitman ML, Smith RG, ET AL. Effects of těžištěm loss and sodium restriction on on on on pioglitazoneinduced fluid retention. CL1; FLT: 0 CL3; CL3; CL3; Diabetes Obes Metab CL1; CL1; FLT: 1 CL3; CL3; 2022; 24 (4): 701-709. CL1; CL1; FLT: 2 CL3; CL3; CL3; htt3F; https: / doi.org / 10.11111 / dom.14630; CL1; CLLLT3; FLT3; FL3;