Metabolic Syndrome and Pharmacological Interventions in Clinical Development
Abstract
1. Introduction
1.1. Atherogenic Dyslipidemia
1.2. Arterial Hypertension
1.3. Management of Hyperglycemia
1.4. Weight Management
2. Material and Methods
3. Results
3.1. Type 2 Diabetes, Obesity and/or Overweight
3.2. Dyslipidemia and Lipoprotein Disorder
3.3. Hypertension
3.4. Metabolic Syndrome and Insulin Resistance
4. Discussion
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Measure | Categorical Cut Points |
---|---|
Elevated waist circumference * | Population- and country-specific definitions |
Elevated triglycerides (drug treatment for elevated triglycerides is an alternate indicator **) | ≥150 mg/dL (1.7 mmol/L) |
Reduced HDL-C (drug treatment for reduced HDL-C is an alternate indicator **) | <40 mg/dL (1.0 mmol/L) in males; <50 mg/dL (1.3 mmol/L) in females |
Elevated blood pressure (antihypertensive drug treatment in a patient with a history of hypertension is an alternate indicator) | Systolic ≥ 130 and/or diastolic ≥ 85 mm Hg |
Elevated fasting glucose *** (drug treatment of elevated glucose is an alternate indicator) | ≥100 mg/dL |
N | Investigational Drug | Mechanism of Action | Indication | Main Site Location | Phase | NCT |
---|---|---|---|---|---|---|
1 | 6-bromotryptophan (6-BT) | Endogenous plasma microbiome-derived tryptophan metabolite | Metabolic Syndrome | USA and/or Europe | Phase 1 Phase 2 | NCT05971524 |
2 | AD-209 | N/A | Essential Hypertension | South Korea | Phase 2 | NCT05631990 |
3 | AD-218 | N/A | Dyslipidemia | South Korea | Phase 3 | NCT05631990 |
4 | AD-221 and AD-221A | N/A | Primary Hypercholesterolemia | China | Phase 3 | NCT05131997 |
5 | AD-223 | N/A | Essential Hypertension | South Korea | Phase 3 | NCT06052748 |
6 | ALN-KHK | RNAi targeting ketohexokinase | Type 2 Diabetes Mellitus with Obesity | USA and/or Europe | Phase 1 Phase 2 | NCT05761301 |
7 | ALT-801 (SP-1373) | Dual GCGR and GLP-1 receptor agonist | Obesity | USA and/or Europe | Phase 2 | NCT05295875 |
8 | AP-325 | Binds and modulates the GABAA receptor (an ionotropic receptor and ligand-gated ion channel) | Type 2 Diabetes Mellitus | USA and/or Europe | Phase 2 | NCT05160272 |
9 | APHD-012 | Distal jejunal-release dextrose | Obesity | USA and/or Europe | Phase 2 | NCT05385978 |
10 | ATB-1011 and ATB-1012 | N/A | Essential Hypertension and Type 2 Diabetes Mellitus | China | Phase 3 | NCT05573477 |
11 | AZD0780 | Oral PCSK9 Inhibitor | Dyslipidemia | USA and/or Europe | Phase 2 | NCT06173570 |
12 | AZD8233 | ASO targeting PCSK9 | Hyperlipidaemia | USA and/or Europe | Phase 2 | NCT04964557, NCT06173570 |
13 | AZD9550 | Dual GCGR and GLP-1 receptor agonist | Type 2 Diabetes Mellitus with Overweight or Obesity | USA and/or Europe | Phase 1 Phase 2 | NCT06151964 |
14 | Baxdrostat (CIN-107) | Aldosterone synthase inhibitors | Uncontrolled Hypertension and Resistant Hypertension; Uncontrolled Hypertension and Chronic Kidney Disease | USA and/or Europe | Phase 2 Phase 3 | NCT06344104, NCT05432167 |
15 | BC Lispro (THDB0206) | Insulin | Type 2 Diabetes Mellitus | China | Phase 3 | NCT05834868 |
16 | Berlim 25/2 | N/A | Type 2 Diabetes Mellitus and Dyslipidemia | Brazil | Phase 3 | NCT04602754 |
17 | Bimagrumab | mAb inhibitor of ActRII | Overweight or Obesity | USA and/or Europe | Phase 2 | NCT05616013 |
18 | BMF-219 | Oral irreversible covalent inhibitor of menin | Type 2 Diabetes Mellitus | USA and/or Europe | Phase 1 Phase 2 | NCT05731544 |
19 | BR1017A and BR1017B | N/A | Essential Hypertension and Primary Hypercholesterolemia | South Korea | Phase 3 | NCT05930028 |
20 | BR1018B and BR1018C | N/A | Essential Hypertension and Primary Hypercholesterolemia | South Korea | Phase 3 | NCT06165250 |
21 | Cagrilintide | Amylin receptor agonist | Type 2 Diabetes Mellitus; Overweight or Obesity | USA and/or Europe | Phase 2 Phase 3 | NCT05813925, NCT04982575 |
22 | CKD-391 and CKD-331 | N/A | Primary Hypercholesterolemia | China, South Korea | Phase 3 | NCT05657574 |
23 | CPL207280 | GPR40 (also known as FFA receptor 1) agonist | Type 2 Diabetes Mellitus | USA and/or Europe | Phase 2 | NCT05248776 |
24 | D064 and D702 | N/A | Essential Hypertension | South Korea | Phase 3 | NCT06121518 |
25 | D150, D745 and D759 | N/A | Type 2 Diabetes Mellitus | South Korea | Phase 3 | NCT05566028 |
26 | Dapiglutide | Dual GLP-1R/GLP-2R agonist | Obesity | USA and/or Europe | Phase 2 | NCT05788601 |
27 | Denatonium Acetate (ARD-101) | Oral potential TAS2R agonist | Obesity | USA and/or Europe | Phase 2 | NCT05121441 |
28 | DW1125 and DW1125A | N/A | Primary Hypercholesterolemia or Dyslipidemia | South Korea | Phase 3 | NCT05970679 |
29 | DWP16001 | SGLT2 inhibitor | Type 2 Diabetes Mellitus | China, South Korea | Phase 3 | NCT05376930, NCT05505994 |
30 | Ecnoglutide (XW003) | Long-acting cAMP Signaling Biased GLP-1 Analog | Obesity; Type 2 Diabetes Mellitus | USA and/or Europe, China | Phase 2 Phase 3 | NCT05111912, NCT05813795, NCT05680155, NCT05680129 |
31 | Efsitora Alfa (BIF, LY3209590, or insulin efsitora alfa) | Basal Insulin Fc | Type 2 Diabetes Mellitus | USA and/or Europe | Phase 3 | NCT05462756 |
32 | GLY-200 | Mucin-complexing polymer | Obesity; Type 2 Diabetes Mellitus | USA and/or Europe | Phase 2 | NCT06259981, NCT05478525 |
33 | GSBR-1290 | Oral GLP-1 receptor agonist | Type 2 Diabetes Mellitus, and Overweight or Obesity | USA and/or Europe | Phase 1 Phase 2 | NCT05762471 |
34 | GZR18 | GLP-1 receptor agonist | Type 2 Diabetes Mellitus; Overweight or Obesity | China | Phase 1 Phase 2 | NCT06256523, NCT06256536, NCT06256562 |
35 | GZR4 | INSR agonist | Type 2 Diabetes Mellitus | China | Phase 2 | NCT06202079 |
36 | HCP1803 | N/A | Essential Hypertension | South Korea | Phase 3 | NCT05362110 |
37 | HCP1904-3 | N/A | Essential Hypertension | South Korea | Phase 3 | NCT05199129 |
38 | HCP2102 | N/A | Essential Hypertension | South Korea | Phase 3 | NCT05450601 |
39 | HD-6277 | Selective GPR40 agonist | Type 2 Diabetes Mellitus | South Korea | Phase 2 | NCT05666128 |
40 | HEC88473 | Dual FGF21 receptor and GLP-1 receptor agonist | Type 2 Diabetes Mellitus | China | Phase 2 | NCT06148649 |
41 | HRS9531 | Dual GIP and GLP-1 receptor agonist | Obesity; Type 2 Diabetes Mellitus | China | Phase 2 | NCT05881837, NCT05966272 |
42 | HS-20094 | Dual GIP and GLP-1 receptor agonist | Type 2 Diabetes Mellitus; Overweight or Obesity | China | Phase 2 | NCT06118008, NCT06118021 |
43 | HSG4112 | Analog of glabridin | Overweight or Obesity | South Korea | Phase 2 | NCT05197556 |
44 | iGlarLixi vs. IDegAsp | Insulins | Type 2 Diabetes Mellitus | China | Phase 3 | NCT05413369 |
45 | INS068 | Long-acting insulin analog | Type 2 Diabetes Mellitus | South Korea | Phase 3 | NCT05702073, NCT05699408 |
46 | Insulin Efsitora Alfa (LY3209590) | Basal Insulin Fc (BIF) | Type 2 Diabetes Mellitus | USA and/or Europe | Phase 3 | NCT05662332, NCT05275400 |
47 | INV-202 | CB1R inverse agonist | Obesity and Metabolic Syndrome; Type 2 Diabetes Mellitus | USA and/or Europe | Phase 2 | NCT05891834, NCT05514548 |
48 | ION904 (IONIS-AGT-LRx) | Hepatocyte-directed ASO targeting AGT mRNA | Uncontrolled Hypertension | USA and/or Europe | Phase 2 | NCT05314439 |
49 | JS002 | Humanized anti-PCSK9 mAb | Hyperlipidaemia | China | Phase 3 | NCT05532800 |
50 | JW0101+C2101 | Livalo (pitavastatin) | Dyslipidemia and Hypertension | South Korea | Phase 3 | NCT05331014 |
51 | JW0201 | N/A | Type 2 Diabetes Mellitus | South Korea | Phase 3 | NCT05814393 |
52 | Lepodisiran (LY3819469) | siRNA (binds to the hepatic asialoglycoprotein receptor) targeting Lp(a) | Elevated Lipoprotein(a) | USA and/or Europe | Phase 2 Phase 3 | NCT05565742, NCT06292013 |
53 | Lerodalcibep (LIB003) | PCSK9 Inhibitor | Hyperlipidaemia and High risk Cardiovascular Disease (CVD) | USA and/or Europe | Phase 3 | NCT05004675, NCT05234775 |
54 | Lorundrostat (MLS-101) | Aldosterone synthase inhibitor | Resistant Hypertension; Uncontrolled Hypertension | USA and/or Europe | Phase 2 Phase 3 | NCT06153693, NCT05968430, NCT05001945 |
55 | Eloralintide (LY3841136) | Amylin receptor agonist | Overweight or Obesity | USA and/or Europe | Phase 2 | NCT06230523 |
56 | MAR001 | Maresin 1 (MaR1) specialised pro-resolving lipid mediator | Metabolic dysfunction at screening (triglyceride levels > 2.8 mmol/L) | USA and/or Europe | Phase 1 Phase 2 | NCT05896254 |
57 | Maridebart cafraglutide (AMG 133) | Dual GIP and GLP-1 receptor agonist | Overweight or Obesity With or Without Type 2 Diabetes Mellitus | USA and/or Europe | Phase 2 | NCT05669599 |
58 | Mazdutide (IBI362, LY3305677) | Dual GCGR and GLP-1 receptor agonist | Type 2 Diabetes Mellitus with Obesity; Overweight or Obesity | USA and/or Europe, China | Phase 2 Phase 3 | NCT06184568, NCT06143956, NCT04904913 |
59 | MBL949 | GDF15 agonist (agonist at the GFRAL/RET receptor) | Obesity with or without Type 2 Diabetes Mellitus | USA and/or Europe | Phase 2 | NCT05199090 |
60 | MK-0616 | Oral PCSK9 inhibitor | Hyperlipidaemia | USA and/or Europe | Phase 3 | NCT05952856 |
61 | Muvalaplin (LY3473329) | Orally active inhibitor of Lp(a) | Elevated Lipoprotein(a) at High Risk for Cardiovascular Events | USA and/or Europe | Phase 2 | NCT05563246 |
62 | NNC0165-1875 | NPY2R or Y2R agonist | Obesity | USA and/or Europe | Phase 2 | NCT04969939 |
63 | NNC0480-0389 | N/A | Type 2 Diabetes Mellitus | USA and/or Europe | Phase 2 | NCT05144984 |
64 | NNC0519-0130 | Dual GIP and GLP-1 receptor agonist | Overweight or Obesity, Type 2 Diabetes Mellitus | USA and/or Europe | Phase 2 | NCT06326060, NCT06326047 |
65 | NST-1024 (SEFA-1024) | CETP inhibitor | Hypertriglyceridemia | USA and/or Europe | Phase 2 | NCT05889156 |
66 | Obicetrapib (AMG-899, DEZ-001, TA-8995) | CETP inhibitor | Hyperlipidaemia; Heterozygous familial hypercholesterolemia (HeFH) and/or atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors | USA and/or Europe | Phase 2 Phase 3 | NCT05421078, NCT06005597, NCT05266586 |
67 | Ocedurenone(KBP-5074) | Third-generation non-steroidal MRA | Uncontrolled Hypertension and Moderate or Severe Chronic Kidney Disease | USA and/or Europe | Phase 3 | NCT04968184 |
68 | Olezarsen (ISIS 678354, AKCEA-APOCIII-LRx) | ASO targeting mRNA for APOC3 | Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia; Severe Hypertriglyceridemia | USA and/or Europe | Phase 3 | NCT05552326, NCT05079919, NCT05610280 |
69 | Olpasiran (AMG-890, ARO-LPA) | siRNA (binds to the hepatic asialoglycoprotein receptor) targeting Lp(a) | Atherosclerotic cardiovascular disease (ASCVD) and elevated Lipoprotein(a). | USA and/or Europe | Phase 3 | NCT05581303 |
70 | Orforglipron (LY3502970) | Non-peptide GLP-1 receptor agonist | Type 2 Diabetes Mellitus with Overweight or Obesity; Type 2 Diabetes Mellitus; Overweight or Obesity and related comorbidities, Overweight or Obesity | USA and/or Europe | Phase 3 | NCT05803421, NCT06010004, NCT05869903, NCT05872620, NCT05051579, NCT05048719 |
71 | PB-201 | Glucokinase activator (partial, pancreas- and liver-dual activator of glucokinase) | Type 2 Diabetes Mellitus | China | Phase 3 | NCT05102149 |
72 | Pegozafermin (BIO89-100) | FGF21 analog | Severe Hypertriglyceridemia | USA and/or Europe | Phase 3 | NCT05852431 |
73 | Pelacarsen (IONIS-APO(a)-LRx, AKCEA-APO(a)-LRx, or TQJ230) | Apo(a) inhibitor, hepatocyte-directed ASO targeting mRNA transcribed from the LPA gene | Hyperlipoproteinemia(a) and Established Cardiovascular Disease | USA and/or Europe | Phase 3 | NCT05305664, NCT05900141 |
74 | Pemafibrate (K-877, LY3473329) | Selective peroxisome proliferator-activated receptor (PPAR)-α modulator (SPPARM) | Hypercholesterolemia and statin intolerance; Elevated Lipoprotein(a) | USA and/or Europe | Phase 2 Phase 3 | NCT05923281, NCT05563246 |
75 | Plozasiran (ARO-APOC3) | siRNA targeting mRNA for APOC3 | Hypertriglyceridemia; Severe Hypertriglyceridemia; Dyslipidemia | USA and/or Europe | Phase 2 Phase 3 | NCT06347133, NCT06347016, NCT05413135, NCT04720534, NCT04998201 |
76 | RAY1225 | Dual GIP and GLP-1 receptor agonist | Type 2 Diabetes Mellitus; Obesity | China | Phase 2 | NCT06254274, NCT06254261 |
77 | Recaticimab (SHR-1209) | mAb against PCSK9 | Hyperlipidaemia | China | Phase 3 | NCT04885218 |
78 | Rilparencel (Renal Autologous Cell Therapy-REACT®) | Renal Autologous Cell Therapy | Type 2 Diabetes Mellitus and Chronic Kidney Disease | USA and/or Europe | Phase 3 | NCT05099770 |
79 | Retatrutide (LY3437943) | Triple GIP, GLP-1 and GCGR receptor agonist | Overweight or Obesity and Chronic Kidney Disease With or Without Type 2 Diabetes Mellitus; Type 2 Diabetes Mellitus; Overweight or Obesity; Type 2 Diabetes Mellitus with Overweight or Obesity; Overweight or Obesity with Cardiovascular Disease | USA and/or Europe | Phase 2 Phase 3 | NCT05936151, NCT06297603, NCT05929066, NCT05929079, NCT05882045, NCT04881760 |
80 | RGT-075 | Oral GLP-1 receptor agonist | Overweight or Obesity | USA and/or Europe | Phase 2 | NCT06277934 |
81 | Solbinsiran (LY3561774) | siRNA that targets ANGPTL3 | Dyslipidemia | USA and/or Europe | Phase 2 | NCT05256654 |
82 | SPC1001 | N/A | Essential Hypertension | South Korea | Phase 2 | NCT06212648 |
83 | SPH3127 | Renin inhibitor (direct) | Essential Hypertension | China | Phase 3 | NCT05359068 |
84 | Supaglutide | GLP-1 receptor agonist | Type 2 Diabetes Mellitus | China | Phase 2 Phase 3 | NCT04994288, NCT04998032 |
85 | Survodutide (BI 456906) | Dual GCGR and GLP-1 receptor agonist | Type 2 Diabetes Mellitus with Overweight or Obesity; Obesity; Overweight or Obesity | USA and/or Europe | Phase 3 | NCT06066528, NCT06176365, NCT06066515, NCT06077864 |
86 | TLC-3595 (S-723595) | Allosteric inhibitor of acetyl-CoA carboxylase 2 (ACC2) | Insulin Resistance | USA and/or Europe | Phase 2 | NCT05665751 |
87 | Trevogrumab (REGN1033) and Garetosmab (REGN2477) | Trevogrumab is GFD8 fully humanized mAb, Garetosmab (REGN2477) Act-A mAb | Obesity | USA and/or Europe | Phase 2 | NCT06299098 |
88 | Vericiguat | Stimulator of soluble guanylate cyclase (sGC) | Metabolic Syndrome and Coronary Vascular Dysfunction | USA and/or Europe | Phase 2 | NCT05711719 |
89 | VK2735 | Dual GIP and GLP-1 receptor agonist | Overweight or Obesity | USA and/or Europe | Phase 2 | NCT06068946 |
90 | XXB750 | mAb, NPR1 agonist | Resistant Hypertension | USA and/or Europe | Phase 2 | NCT05562934 |
91 | Yogliptin | DPP-4 inhibitor | Type 2 Diabetes Mellitus | China | Phase 3 | NCT05318326 |
92 | Zerlasiran (SLN360) | siRNA (binds to the hepatic asialoglycoprotein receptor) targeting Lp(a) | Elevated lipoprotein(a) at high risk of atherosclerotic cardiovascular disease events | USA and/or Europe | Phase 2 | NCT05537571 |
93 | Zilebesiran (ALN-AGT) | siRNA targeting AGT mRNA | High cardiovascular risk and Uncontrolled Hypertension; Hypertension | USA and/or Europe | Phase 2 | NCT06272487, NCT04936035, NCT05103332 |
94 | Zodasiran (ARO-ANG3) | siRNA that targets ANGPTL3 | Dyslipidemia | USA and/or Europe | Phase 2 | NCT04832971 |
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Javor, E.; Šarčević, D.; Rešić, A. Metabolic Syndrome and Pharmacological Interventions in Clinical Development. Diabetology 2024, 5, 300-320. https://doi.org/10.3390/diabetology5030023
Javor E, Šarčević D, Rešić A. Metabolic Syndrome and Pharmacological Interventions in Clinical Development. Diabetology. 2024; 5(3):300-320. https://doi.org/10.3390/diabetology5030023
Chicago/Turabian StyleJavor, Eugen, David Šarčević, and Arnes Rešić. 2024. "Metabolic Syndrome and Pharmacological Interventions in Clinical Development" Diabetology 5, no. 3: 300-320. https://doi.org/10.3390/diabetology5030023
APA StyleJavor, E., Šarčević, D., & Rešić, A. (2024). Metabolic Syndrome and Pharmacological Interventions in Clinical Development. Diabetology, 5(3), 300-320. https://doi.org/10.3390/diabetology5030023