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Therapeutics for type-2 diabetes mellitus: a glance at the recent inclusions and novel agents under development for use in clinical practice.

ABSTRACT: Diabetes mellitus (DM) is a chronic, progressive, and multifaceted illness resulting in significant physical and psychological detriment to patients. As of 2019, 463 million people are estimated to be living with DM worldwide, out of which 90% have type-2 diabetes mellitus (T2DM). Over the years, significant progress has been made in identifying the risk factors for developing T2DM, understanding its pathophysiology and uncovering various metabolic pathways implicated in the disease process. This has culminated in the implementation of robust prevention programmes and the development of effective pharmacological agents, which have had a favourable impact on the management of T2DM in recent times. Despite these advances, the incidence and prevalence of T2DM continue to rise. Continuing research in improving efficacy, potency, delivery and reducing the adverse effect profile of currently available formulations is required to keep pace with this growing health challenge. Moreover, new metabolic pathways need to be targeted to produce novel pharmacotherapy to restore glucose homeostasis and address metabolic sequelae in patients with T2DM. We searched PubMed, MEDLINE, and Google Scholar databases for recently included agents and novel medication under development for treatment of T2DM. We discuss the pathophysiology of T2DM and review how the emerging anti-diabetic agents target the metabolic pathways involved. We also look at some of the limiting factors to developing new medication and the introduction of unique methods, including facilitating drug delivery to bypass some of these obstacles. However, despite the advances in the therapeutic options for the treatment of T2DM in recent years, the industry still lacks a curative agent.

SUBMITTER: Shah N

PROVIDER: S-EPMC8474306 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background SGLT-2 (sodium glucose transporter-2) inhibitors and GLP-1RAs (glucagon-like peptide-1 receptor agonists) effectively lowered cardiovascular risk in large clinical trials for patients with type 2 diabetes mellitus at high risk for these complications, and have been recommended by guidelines. To evaluate the contemporary landscape in which these recommendations would be implemented, we examined the use of these medications according to clinical guideline practice. Methods and Results In the National Health and Nutrition Examination Survey for 2017 to 2018, we defined compelling indications for SGLT-2 inhibitors by the presence of atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, and for GLP-1RAs by the presence of established or high-risk atherosclerotic cardiovascular disease, based on large clinical trials that have been incorporated in guideline recommendations of the American College of Cardiology and American Diabetes Association. We then evaluated use of these medications among patients with physician-diagnosed type 2 diabetes mellitus. All analyses incorporated complex survey design to produce nationally representative estimates. A total 1104 of 9254 sampled individuals had type 2 diabetes mellitus, representing 10.6% (95% CI, 9.7%-11.6%) of the US population or 33.2 million adults nationally. Of these, 52.6% (95% CI, 47.7%-57.5%) had an indication for SGLT-2 inhibitors, 32.8% (95% CI, 28.8%-37.2%) for GLP-1RAs, and 26.6% (95% CI, 22.2%-31.7%) for both medications. During 2017 to 2018, 4.5% (95% CI, 2.4%-8.2%) were treated with SGLT-2 inhibitors and 1.5% (95% CI, 0.7%-3.2%) with GLP-1RAs. Atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease were not independently associated with SGLT-2 inhibitor or GLP-1RA use in patients with diabetes mellitus. Conclusions Despite a large number of patients being eligible for guideline-recommended cardiorenal protective therapies, there are substantial gaps in the use of SGLT-2 inhibitors and GLP-1RAs, limiting their public health benefits.

Project description:Diabetes mellitus (DM) affects hundreds of million people worldwide and the impaired bone healing is an important DM-related complication. Understanding how DM affects the activities of osteoclasts and the underlying mechanisms is crucial to the development of effective approaches for accelerating bone healing in DM condition. To date, however, the influence of DM on osteoclasts remains obscure and controversial. In this study, we established a type 2 DM (T2DM) alveolar bone defect model, which closely simulates the pathogenesis of human T2DM, to explore the diabetic osteoclast activity during bone regeneration. We found that a high glucose concentration diminished the formation of osteoclasts, and the differentiation and function of osteoclasts from T2DM rats were suppressed. The degradation of matrix by osteoclasts was significantly reduced at a high glucose concentration. In vivo experiments further indicated that T2DM inhibited osteoclastogenesis and osteoclast activity, and delayed the degradation of matrix during the alveolar bone regeneration in T2DM rats. Our work clarifies the influence of T2DM on osteoclasts, and provides valuable insights for the design of novel scaffolding materials that target on osteoclasts for T2DM bone regeneration. STATEMENT OF SIGNIFICANCE: Impaired bone healing is one of the diabetes mellitus (DM)-related complications. Understanding how DM affects osteoclast activity and scaffolding matrix degradation is pivotal to the development of effective approaches for accelerating bone healing in DM condition. Currently, the influences of DM on osteoclast activity and matrix degradation in bone defect areas, however, remain controversial and obscure. Herein, we established a type 2 DM (T2DM) alveolar bone defect model and our results show that T2DM inhibited osteoclastogenesis and osteoclast activity, and delayed the degradation of scaffolding matrix. Our work clarifies the influence of T2DM on osteoclasts and matrix degradation, and provides insights for the design of novel scaffolding materials that target on osteoclasts for T2DM bone regeneration.

Project description:BackgroundPrevious studies of inter-practice variation of the prevalence of hypertension and diabetes mellitus showed wide variations between practices. However, in these studies inter-practice variation was calculated without controlling for clustering of patients within practices and without adjusting for patient and practice characteristics. Therefore, in the present study inter-practice variation of diagnosed hypertension and diabetes mellitus prevalence rates was calculated by 1) using a multi-level design and 2) adjusting for patient and practice characteristics.MethodsData were used from the Netherlands Information Network of General Practice (LINH) in 2004. Of all 168.045 registered patients, the presence of hypertension, diabetes mellitus and all available ICPC coded symptoms and diseases related to hypertension and diabetes, were determined. Also, the characteristics of practices were used in the analyses. Multilevel logistic regression analyses were performed.ResultsThe 95% prevalence range for the practices for the prevalence of diagnosed hypertension and diabetes mellitus was 66.3 to 181.7 per 1000 patients and 22.2 to 65.8 per 1000 patients, respectively, after adjustment for patient and practice characteristics. The presence of hypertension and diabetes was best predicted by patient characteristics. The most important predictors of hypertension were obesity (OR = 3.5), presence of a lipid disorder (OR = 3.0), and diabetes mellitus (OR = 2.6), whereas the presence of diabetes mellitus was particularly predicted by retinopathy (OR = 8.5), lipid disorders (OR = 2.8) and hypertension (OR = 2.7).ConclusionAlthough not the optimal case-mix could be used in this study, we conclude that even after adjustment for patient (demographic variables and risk factors for hypertension and diabetes mellitus) and practice characteristics (practice size and presence of a practice nurse), there is a wide difference between general practices in the prevalence rates of diagnosed hypertension and diabetes mellitus.

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Therapeutics for type-2 diabetes mellitus: a glance at the recent inclusions and novel agents under development for use in clinical practice.

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