Table 2.
Currently developing drugs targeting insulin resistance.
| Targets | Starting time | Phase | Condition or disease | Intervention | Treatment schedule | Primary outcome measures | Secondary Endpoints: | Study design | NCT number |
|---|---|---|---|---|---|---|---|---|---|
| microbial gut | 2020 | Phase 4 | Obesity Insulin Resistance |
Dietary Supplement: Synbiotic (Rillus) Drug: Placebo |
12weeks | HOMA-IR | Abundance-based Coverage Estimator (ACE) Index of Faecal Sample; Shannon Index of Faecal Sample | A multiple-arm, non-Randomized study | NCT04642482 |
| PPAR-α/δ agonist | 2011 | Phase 2 | Insulin Resistance Abdominal Obesity |
Drug: GFT505 80mg Drug: Placebo |
8-week treatment period, a 6-week wash out period, a second 8-week treatment period; hard gelatin capsules dosed at 20mg, oral administration, 4 capsules per day before breakfast | Glucose Infusion Rate (GIR) | Differences in Hepatic Glucose Production (HGP); Changes in HGP (Hepatic Glucose Production) | A Multicentre, Randomised, Single Blind, Placebo-Controlled, Cross Over Study. | NCT01271777 |
| PPAR-γ agonist | 2021 | Phase 2 | Prostate Cancer Insulin Resistance |
Drug: Pioglitazone 30 mg Drug: placebo tablet |
Subjects will self-administer a 30 mg pioglitazone oral tablet daily For patient taking a diabetic regimen of gemfibrozil, the dose will be 15 mg daily; 6 months. |
insulin sensitivity | Insulin signaling | A prospective, randomized, double-blind, placebo-controlled trial | NCT04995978 |
| Intestinal microbiota | 2016 | Phase 2 | Obesity, Morbid Insulin Resistance |
Biological: Fecal filtrate from 150 g stool from healthy lean donors Biological: Fecal filtrate from 150 g of the recipient’s own stool |
150 g stool from healthy lean donors will be diluted in 0.9% normal saline to a total volume of 450 mL; 12 weeks | HOMA-IR | Body weight, BMI, %weight change, appetite score, quality of life questionaire, depression score, anxiety score | A randomized controlled trial | NCT02970877 |
| NLRP3 inflammasome | 2021 | Phase 2 | Obesity Insulin Resistance Inflammation |
Drug: Colchicine Drug: Placebo |
Colchicine 1 capsule (0.6 mg) per day; 12 weeks | HOMA-IR | Fasting serum insulin, fasting serum glucose, High-Sensitivity C-Reactive Protein, Matsuda Index | A randomized, Controlled Trial | NCT05017571 |
| LDL receptor | 2013 | Phase 3 | Metabolic Syndrome X | Drug: Ezetimibe Drug: Placebo |
Ezetimibe 10 mg/d; 12 weeks | Change in Intestinal mRNA Expression Levels of LDL Receptor | Change in Intestinal mRNA Expression Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA; Change in Intestinal Protein Levels of LDL Receptor; Change in Protein Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase | Randomized; Crossover Assignment | NCT01849068 |
| renal SGLT2 | 2015 | Phase 4 | Type 2 Diabetes Mellitus | Drug: Dapagliflozin Drug: Placebo |
Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks | Adjusted Change From Baseline in Skeletal Muscle Insulin-stimulated Gluocose Uptake | Adjusted Change in Adipose Tissue Insulin-stimulated Glucose Uptake; Adjusted Change in Liver Insulin-stimulated Glucose Uptake | single centre, randomized, parallel-group, double-blind, placebo-controlled Phase IV study | NCT02426541 |
| PDE5 i | 2015 | Phase 2 | Type 2 Diabetes Mellitus | Drug: Tadalafil Drug: Placebo |
Per oral intake of tadalafil 20 mg o.d.; six weeks | insulin sensitivity (glucose disposal rate) | Mean glucose (HbA1c, mmol/mol) in blood; Fasting plasma glucose levels; Arginine-induced insulin secretion (area under curve, AUC, mU/l/min); Levels interstitial insulin; Lactate concentrations in insulin sensitive tissues; Levels of inflammatory markers in blood; Endothelial function in peripheral arteries measured with EndoPAT, | a double-blind, placebo-controlled crossover study | NCT02601989 |
| PI3-kinase, Akt, GLUT-4, PPAR-γ, and PPARδ |
2013 | Phase 3 | Polycystic Ovary Syndrome (PCOS) Insulin Resistance |
Drug: DLBS3233 Drug: Metformin XR Drug: Placebo metformin Drug: Placebo DLBS3233 |
DLBS3233 100 mg capsule once daily; Metformin XR 750 mg caplet twice daily, | HOMA-IR | Lipid profile improvement; Improvement of glucose tolerance; Change of waist circumference; Response rate: presence of ovulation; Change of endometrium thickness; mprovement of S/A ratio; Improvement in Ferriman-Gallwey Score; Reduction of free testosterone level; Change of luteinizing hormone (LH) level; Change of luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio | 3-arm, randomized, double-blind, double-dummy, and controlled clinical study | NCT01999686 |
| angiotensin-receptor blocking (ARB) | 2014 | Phase 4 | Essential Hypertension Complicated by Type 2 Diabetes Mellitus | Drug: Azilsartan Drug: Telmisartan |
azilsartan 20 mg once daily in the morning; 12 weeks | Change in Insulin Resistance Index (HOMA-R) | Change in Fasting Blood Glucose; Change in Fasting Insulin; Change in Glycosylated Hemoglobin (HbA1c); Change in Homeostasis Model Assessment of Beta Cell Function (HOMA-β); Change in 1,5-anhydroglucitol (1,5-AG); Number of Participants With Treatment-Emergent Adverse Events | Multicenter, randomized, open-label, parallel-group exploratory study | NCT02079805 |
| amino acid | 2021 | Not Applicable | Obesity Insulin Resistance |
Dietary Supplement: Oral glutamine supplementation Dietary Supplement: Oral protein powder supplementation |
oral glutamine supplementation 10 g Ter In Die; 8 weeks | HOMA-IR | Irritable Bowel Syndrome (IBS) severity score; feces consistency | a blinded randomized controlled trial | NCT04883515 |
| bariatric procedures | 2017 | Not Applicable | Insulin Resistance Obesity |
Procedure: Roux-en-Y Gastric Bypass (RYGBP) Procedure: Sleeve Gastrectomy (SG) Behavioral: Very Low Calorie Diet (VLCD) |
standard RYGBP procedure; standard SG procedure | Change in urine free cortisol level | a non-randomized prospective study | NCT03371368 | |
| lifestyle intervention | 2022 | Not Applicable | Diabetes Mellitus, Type 2 Insulin Resistance |
Procedure: Passive heating Procedure: Thermoneutral |
perform baths in 38°C natural thermal mineral water a maximum of five times per week; 12 weeks | Change in hemoglobin A1c level | Change in fasting plasma glucose; Change in fasting insulin; HOMA-IR; Decrease of daily insulin dose; BMI; Change in mean blood pressure; Change in heart output; Change in the prevalence of electrocardiogram events; Change in the proportion of hypertension, retinopathy, nephropathy, neuropathy; Change in total cholesterol level, LDL level, HDL level, triglyeride level, ALP, ALT, AST, GGT, glomerular filtration rate, creatinine level, etc. | a two-arm, randomized, controlled study | NCT05237219 |
| antioxidation | 2020 | Not Applicable | Non-Alcoholic Fatty Liver Disease Insulin Resistance |
Drug: Nutraceutical therapy | Oral administration of 303mg of silybin-phospholipid complex, 10mg of vitamin D, and 15mg of vitamin E, twice a day; six months | HOMA-IR | Mean change in ALT levels, insulin levels, CRP levels, TBARS levels | randomized; open label, parallel assignment | NCT04640324 |
| electrical stimulation | 2019 | Not Applicable | Obesity Overweight Insulin Resistance |
Device: Neuromuscular Electrical Stimulation (Sensory) Device: Neuromuscular Electrical Stimulation Other: Resistance Training |
Group will receive Electrical Stimulation up to maximum tolerable level (30min/day, 3x/week); 8 weeks | Glycemic Control | Respiratory Exchange Ratio; Amount of lean mass | Randomized; Parallel Assignment | NCT03947697 |