What is on the horizon for type 2 diabetes pharmacotherapy? – An overview of the antidiabetic drug development pipeline

Johansson, Karl Sebastian; Sonne, David P.; Knop, Filip K.; Christensen, Mikkel B.

doi:10.1080/17460441.2020.1791078

Cited by 8 publications

(4 citation statements)

References 110 publications

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“…In theory, a combination of different gut hormone receptor agonists, which targets multiple systems simultaneously, may replicate the gut hormone milieu after bariatric surgery and circumvent the counter‐regulatory adaptive changes associated with dietary energy restriction. An increasing number of preclinical and early‐phase clinical trials have revealed the potential of additive benefits obtained with dual or triple gut peptide receptor agonists in reducing body weight and improving associated conditions such as hepatic steatosis or type 2 diabetes 191 …”

Section: Pathophysiology Of Obesity In Humansmentioning

confidence: 99%

An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight

Theilade

Christensen

Vilsbøll

et al. 2021

Diabetes Obesity Metabolism

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Obesity is one of the biggest health challenges of the 21st century, already affecting close to 700 million people worldwide, debilitating and shortening lives and costing billions of pounds in healthcare costs and loss of workability. Body weight homeostasis relies on complex biological mechanisms and the development of obesity occurs on a background of genetic susceptibility and an environment promoting increased caloric intake and reduced physical activity. The pathophysiology of common obesity links neuro‐endocrine and metabolic disturbances with behavioural changes, genetics, epigenetics and cultural habits. Also, specific causes of obesity exist, including monogenetic diseases and iatrogenic causes. In this review, we provide an overview of obesity mechanisms in humans with a focus on energy homeostasis, endocrine regulation of food intake and eating behavior, as well as the most common specific causes of obesity.

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Section: Pathophysiology Of Obesity In Humansmentioning

confidence: 99%

An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight

Theilade

Christensen

Vilsbøll

et al. 2021

Diabetes Obesity Metabolism

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“…MB07803 has better pharmacokinetic properties than CS-917, including higher oral bioavailability, longer active metabolite half-life, and lower inactive N -acetylated metabolite production. Six phase 1 clinical trials and one phase 2a clinical trial on MB07803 have been done [ 148 ]. MB07803 exhibited good safety and tolerability in healthy volunteers (in phase 1 clinical trials) and patients with T2DM (in phase 2a clinical trials).…”

Section: The Clinical Application Of Mir-26 Target Genes With a Focus...mentioning

confidence: 99%

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7

Chen,

Wu,

et al. 2024

Cardiovasc Diabetol

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Atherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3β, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1β, IL-6, JAG2, KCNJ2, MALT1, β-MHC, NF-κB, PCK1, PLCβ1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.

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“…The mechanisms underlying the improvement in insulin sensitivity after IMEG administration are not well understood; they may be due to effects on glucose transporter-4 (Glut-4) and insulin receptor autophosphorylation (IRS). Pacini et al [8] showed that IMEG has SGLT-2 -canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, remogliflozin and tofogliflozin) [5].…”

Section: Effects On Insulin Sensitivitymentioning

confidence: 99%

Imeglimin: a new antidiabetic drug with potential future in the treatment of patients with type 2 diabetes

Nowak

Grzeszczak

2022

Endokrynol Pol

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is multidirectional therapeutic intervention, including both carbohydrate and lipid control and normalization of blood pressure. This strategy has been shown to be beneficial for diabetic patients and contributes to the reduction of total mortality, cardiovascular deaths, and the risk of microangiopathy [3,4].In recent years, several new drugs have been added to the treatment of T2DM, and others are being intensively studied in experimental or clinical trials, producing not only hypoglycaemic effects but also affecting metabolic comorbidities. These include the following: -type II activin receptor modulators (bimagrumab); -amylin or dual amylin-calcitonin receptor agonists (pramlintide -amylin agonist); -adenosine monophosphate-activated protein kinase (AMPK) activator (A-769,662, thienopyridone); -fibroblast growth factor 21 analogues (pegbelfermin), fructose-1,6-bisphosphatase inhibitors (VK0612; MB07803); -novel GLP-1 receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lyxisenatide, semaglutide, efpeglenatide, glutazumab, ITCA-650); -sodium-glucose co-transporters (SGLT-1 and -2) (SGLT-1 -licogliflozin, sotagliflozin and LX2761;

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What is on the horizon for type 2 diabetes pharmacotherapy? – An overview of the antidiabetic drug development pipeline

Cited by 8 publications

References 110 publications

An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight

An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7

Imeglimin: a new antidiabetic drug with potential future in the treatment of patients with type 2 diabetes

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