Switching basal insulins in type 2 diabetes: practical recommendations for health care providers

<p>Basal insulin remains the mainstay of treatment of type 2 diabetes when diet changes and exercise in combination with oral drugs and other injectable agents are not sufficient to control hyperglycemia. Insulin therapy should be individualized, and several factors influence the choice of basal insulin; these include pharmacological properties, patient preferences, and lifestyle, as well as health insurance plan formularies. The recent availability of basal insulin formulations with longer durations of action has provided further dosing flexibility; however, patients may need to switch agents throughout therapy for a variety of personal, clinical, or economic reasons. Although a unit-to-unit switching approach is usually recommended, this conversion strategy may not be appropriate for all patients and types of insulin. Glycemic control and risk of hypoglycemia must be closely monitored by health care providers during the switching process. In addition, individual changes in care and formulary coverage need to be adequately addressed in order to enable a smooth transition with optimal outcomes.</p

Empagliflozin: Role in Treatment Options for Patients with Type 2 Diabetes Mellitus

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s13300-016-0211-x"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p> <p> </p> <p> </p

Dulaglutide in the treatment of adult type 2 diabetes: a perspective for primary care providers

<p>Approximately 90% of T2D patients in the US are diagnosed and treated in the primary care setting, and the majority of the burden of disease management falls to primary care providers. Here, we discuss the clinical data for once weekly dulaglutide, e.g. the results of seven completed Phase 3 trials, patient preference studies, patient reported outcomes (PRO), and clinical data surrounding the dulaglutide administration device. Dulaglutide 1.5 mg once weekly demonstrated superiority to placebo, metformin, sitagliptin, exenatide BID, and insulin glargine (in 2 trials), and non-inferiority to liraglutide in reduction of HbA1c from baseline, with an acceptable safety profile. Dulaglutide-treated patients achieved the composite endpoint of an HbA1c <7.0% with no hypoglycemia, no severe hypoglycemia, and no weight gain significantly more than metformin, sitagliptin, exenatide BID or insulin glargine treated patients. Dulaglutide consistently showed an early onset of glycemic control, lasting up to 104 weeks. Additionally, PRO and patient preference data support the benefit of once weekly dulaglutide for the treatment of T2D.</p

Anhydrous Tetramethylammonium Fluoride for Room-Temperature S_NAr Fluorination

This paper describes the room-temperature S_NAr fluorination of aryl halides and nitroarenes using anhydrous tetramethylammonium fluoride (NMe₄F). This reagent effectively converts aryl-X (X = Cl, Br, I, NO₂, OTf) to aryl-F under mild conditions (often room temperature). Substrates for this reaction include electron-deficient heteroaromatics (22 examples) and arenes (5 examples). The relative rates of the reactions vary with X as well as with the structure of the substrate. However, in general, substrates bearing X = NO₂ or Br react fastest. In all cases examined, the yields of these reactions are comparable to or better than those obtained with CsF at elevated temperatures (i.e., more traditional halex fluorination conditions). The reactions also afford comparable yields on scales ranging from 100 mg to 10 g. A cost analysis is presented, which shows that fluorination with NMe₄F is generally more cost-effective than fluorination with CsF

Understanding concentrated insulins: a systematic review of randomized controlled trials

<p><b>Objective:</b> To compile, analyze, and summarize the literature on concentrated insulins (i.e. concentrations >100 units/mL) from randomized controlled trials and derive guidance on appropriate use of these agents.</p> <p><b>Methods:</b> Searches were conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, Trialtrove (through April 2016) and ClinicalTrials.gov (through April 2017) for phase 1–4 clinical studies using concentrated insulins. Selected studies included multiple-arm, randomized controlled trials evaluating subcutaneously administered concentrated insulins. Trial registration numbers (selected studies) were searched in Medline, Embase and Google Scholar (through April 2017). Late-phase studies were graded using guidance from the Agency for Healthcare Research and Quality.</p> <p><b>Results:</b> Thirty-eight completed trials (7900 participants) and 34 qualifying publications were identified. Four marketed concentrated insulins were evaluated: two long-acting basal (insulin glargine 300 units/mL and insulin degludec 200 units/mL [IDeg200]), one rapid-acting prandial (insulin lispro 200 units/mL [ILis200]), and one prandial/basal (human regular insulin 500 units/mL). Early-phase trials established bioequivalence for IDeg200 and ILis200 with the corresponding 100 units/mL formulations. Efficacy studies showed noninferior glycemic control between comparators for long-acting basal and prandial/basal products with generally low severe hypoglycemia. Six additional concentrated insulins with completed early-phase development were also identified.</p> <p><b>Conclusion:</b> Concentrated-insulin products demonstrated efficacious and safe outcomes in appropriate patients. Clinical findings (HbA1c and hypoglycemia) and methodology (initiation and titration), patient factors (insulin experience and dosing requirements) and treatment characteristics (bioequivalence, potency and device features) are important considerations. This overview of these and other factors provides essential information and guidance for using concentrated insulins in clinical practice.</p

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers

   This article reviews the efficacy and safety data of tirzepatide, a once-weekly, novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist approved in the United States, the European Union, and other regions for the treatment of type 2 diabetes. All doses of tirzepatide demonstrated superiority in reducing A1C and body weight from baseline versus placebo or active comparators. The safety profile of tirzepatide was consistent with that of the GLP-1 receptor agonist class, with mild to moderate and transient gastrointestinal side effects being the most common adverse events. With clinically and statistically significant reductions in A1C and body weight without increased risk of hypoglycemia in various populations, tirzepatide has demonstrated potential as a first-in-class treatment option for many people with type 2 diabetes.</p

Developing Efficient Nucleophilic Fluorination Methods and Application to Substituted Picolinate Esters

This report describes nucleophilic fluorination of 3 and 5-substituted picolinate ester substrates using potassium fluoride in combination with additive promoters. Agents such as tributylmethylammonium or tetraphenylphosphonium chloride were among the best additives investigated giving improved fluorination yields. Additionally, the choice of additive promoters could influence the potential formation of new impurities such as alkyl ester exchange. Other parameters explored in this study include additive stoichiometry, temperature influence on additive degradation, solvent selection, product isolation by solvent extraction, and demonstration of additive recycling