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The Management of Patients with Heart Failure and Diabetes
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
The dipeptidyl peptidase-4 (DPP-4) inhibitors, saxagliptin and alogliptin, have been associated with an increased risk of HF hospitalizations, prompting a statement from the Food and Drug Administration.74–77 The American Heart Association issued a scientific statement stating that saxagliptin may worsen myocardial dysfunction.78 Although DPP-4 inhibitors increase GLP-1, they also increase the expression of stromal cell-derived factor-1, leading to cardiac fibrosis.79
Managing Diabetes and Prediabetes
Published in Ruth Chambers, Paula Stather, Tackling Obesity and Overweight Matters in Health and Social Care, 2022
The ideal drug to manage type 2 diabetes should encourage weight loss and not cause hypoglycaemia. Here are a few examples: Metformin. This low-cost drug has been available in the UK for over 60 years and remains the preferred first choice for newly diagnosed patients with type 2 diabetes.Glucagon-linked peptide (GLP) 1 analogue. These injections can be administered twice a day, once a day or once a week.Sodium glucose co-transporter 2(SGLT2) inhibitor works by preventing the kidneys from reabsorbing glucose back into the blood. Sulfonylureas and insulin commonly cause weight gain, and weight gain is a recognised side effect of pioglitazone. Dipeptidyl peptidase-4 (DPP4) inhibitors are weight neutral.
1,3-Diphenyl-2-Propene-1-One-Based Natural Product Antidiabetic Molecules as Inhibitors of Protein Tyrosine Phosphatase-1B (PTP-1B)
Published in Debarshi Kar Mahapatra, Cristóbal Noé Aguilar, A. K. Haghi, Applied Pharmaceutical Practice and Nutraceuticals, 2021
Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Vivek Asati
In the pharmacotherapeutic point of view, insulin sensitizers are the best compounds for the successful treatment of the hyperglycemic conditions that will amplify the muscle and adipose tissue’s sensitivity to insulin.8 In the modern era, glitazones and sulfonylureas are not much effective in the management of hyperglycemic episodes and therefore the need for effective inhibitors is a major challenge.9 For diabetotherapy, protein tyrosine phosphatase-1B (PTP-1B) inhibitors and dipeptidyl Peptidase-4 (DPP-4) inhibitors are the upcoming preferred options as these compounds prevent the degradation of insulin and prolong the action.10
The role of Recent Pharmacotherapeutic Options on the Management of Treatment Resistant Type 2 Diabetes
Published in Expert Opinion on Pharmacotherapy, 2022
Jeffrey M. Kroopnick, Stephen N. Davis
Hemoglobin A1c (HbA1c) is considered the primary biochemical marker of glycemic control in diabetes though no such consensus exists as to a threshold for ‘poorly controlled [3].’ Often, a HbA1c >7% may be used to define suboptimal control since the American Diabetes Association and European Association for the Study of Diabetes (EASD) recommend HbA1c values of <8% for a majority of patients, taking into account their comorbidities. Achieving an individual’s HbA1c target becomes increasingly difficult due to the natural progressive nature of diabetes mellitus even with escalation of therapy [5]. While no such formal definition exists, Scheen proposed defining treatment-resistant diabetes as persistent poorly controlled diabetes mellitus despite triple oral therapy, which includes the combination of metformin, sulfonylurea, and another oral glucose-lowering agent [6]. However, for the purpose of this review, we define treatment-resistant type 2 diabetes to include patients with suboptimal glycemic control despite the use of at least two maximally tolerated anti-diabetic medications, and these agents may be oral, non-insulin injectables, or insulin. In one study, only 7.3% of the patients on multiple oral medications, primarily metformin, sulfonylureas, and dipeptidyl peptidase-4 (DPP4) inhibitors, achieved a HbA1c >7% [7].
TGR5 agonists for diabetes treatment: a patent review and clinical advancements (2012-present)
Published in Expert Opinion on Therapeutic Patents, 2022
Rachana S. Bhimanwar, Amit Mittal
Kanazawa University conducted a Phase 4 clinical trial on Ursodeoxycholic Acid (UDCA) (21) addressing Glucagon-like peptide-1 (GLP-1) levels (Figure 19). Researchers studied the efficacy and safety of UDCA in people with Type 2 diabetes and chronic liver diseases. Participants (around 16) were administered 900 mg of UDCA for 12 weeks followed by 50 mg of sitagliptin as additive therapy for dipeptidyl peptidase-4 (DPP4) inhibitors. Results showed a decrease in body weight from 72.5 ± 8.4 to 70.6 ± 8.6 kg) and the HbA1c level (7.0%±0.3% to 6.4%±0.5%) in the patients treated with UDCA. The HbA1c level decreased further (6.4% ± 0.5% to 6.0% ± 0.4%) in patients treated with sitagliptin as add-on therapy. A combination of UDCA and the dipeptidyl peptidase-4 inhibitor can therefore be considered a novel treatment of Type 2 diabetes [49,50].
Euglycaemic diabetic ketoacidosis as a complication of SGLT-2 inhibitors: epidemiology, pathophysiology, and treatment
Published in Expert Opinion on Drug Safety, 2020
Erasmia Sampani, Pantelis Sarafidis, Aikaterini Papagianni
In contrast to the above, data from major randomized controlled trials suggested that the incidence of DKA with the use of SGLT-2 inhibitors with T2DM was low (Table 1). Of note, in the majority of cases, clinical trials recorded events of DKA and not specifically euDKA. In the EMPA-REG OUTCOME trial, the frequency of reported events of DKA was less than 0.1% [17]. A meta-analysis from randomized controlled trials at that time showed that SGLT-2 inhibitors were not significantly associated with an increased risk of DKA when compared to placebo or dipeptidyl peptidase 4 (DPP-4) inhibitors [34]. An analysis of all serious adverse events of DKA including 17,596 patients from randomized studies of canagliflozin [35] showed an incidence rate of 0.763 per 1,000 patient-years for those treated with the high dose of canagliflozin (300 mg/day), consistent with observational data in the general population with T2DM [2]. Similarly, in the CANVAS trial [18] a small number of DKA was observed with canagliflozin and placebo (0.6 vs. 0.3 per 1000 patient-years, HR: 2.33, 95% CI 0.76 to 7.17).