Since 2002, AWMSG has acted as a national medicines optimisation committee in Wales. From the outset, pharmacists and clinical pharmacologists have collaborated closely and shared their complementary expertise to make a much greater contribution to the safe, effective, and cost‐effective use of medicines than either group could have achieved by working separately (British Journal of Clinical Pharmacology)
Diabetes News
Category: Pharmacology
Facing the tidal wave De-risking pharma and creating value for patients
This paper examines some of the underlying drivers of the ‘tidal wave’ of diseases, illustrates an alternative way of thinking about the demand challenges and suggest some emerging ways in which industry and the healthcare system can address them (Deloitte)
The placebo response of injectable GLP-1 receptor agonists vs. oral DPP-4 inhibitors and SGLT-2 inhibitors: a systematic review and meta-analysis
The response to placebo treatment was related to its active comparator, with injectable placebo GLP-1ra showing a relevant response on weight, whereas oral placebo DPP4i showed no significant response. These findings may suggest that subjective expectations influence T2DM treatment efficacy, which can possibly be employed therapeutically (British Journal of Clinical Pharmacology)
The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation
Dissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action (Diabetes Care)
Pharmacokinetics and Pharmacodynamics of Insulin Glargine Given Evening as Compared With Morning in Type 2 Diabetes Mellitus
The PD of insulin glargine differs depending on time of administration. With morning administration insulin activity is greater in the first 0–12 h, while with evening administration the activity is greater in the 12–24 h period following dosing (Diabetes Care)
Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events, and incident cancer
There was an association between increasing exogenous insulin dose and increased risk of all-cause mortality, cancer and MACE in people with type 2 diabetes. Limitations of observational studies mean that this should be further investigated using an interventional study design (Diabetes, Obesity and Metabolism)
Glucose Counterregulation in Advanced Type 2 Diabetes Mellitus: Effect of ß-Adrenergic Blockade
Overall glucose counterregulation is preserved in advanced T2DM, but the contribution of EGP is diminished. ß-Adrenergic blockade may increase insulin sensitivity at normoglycemia but does not impair glucose counterregulation in T2DM patients, even those with advanced ß-cell failure (Diabetes Care)
Proinsulin-Transferrin Fusion Protein – a Novel Long-acting Insulin Analogue
ProINS-Tf exhibited a slow, but sustained, in vivo hypoglycemic efficacy and long plasma half-life. Thus, ProINS-Tf fusion protein can potentially be administered as a prodrug with sustained Tf-mediated activation and selectivity in inhibiting hepatic glucose production (Diabetes)
Diabetes drugs affect hearts of men, women differently
In particular, the commonly prescribed diabetes drug metformin had positive effects on heart function in women but not in men, who experienced a shift in metabolism thought to increase the risk of heart failure (Washington University School of Medicine)
DPP-4 inhibitors & GLP-1 reduction in MI size is glucose-dependent
We find that chronic treatment with DPP-4 inhibitors reduced MI size, via the GLP-1 receptor-PKA pathway, in a glucose-dependent manner. Glucose-sensitive cardioprotection of endogenous GLP-1 in diabetic patients may in part explain why intensive control of serum glucose levels has been associated with increased cardiovascular risk (Cardiovascular Diabetology)
Diabetes treatments and cancer risk: drug exposure
In this Review, we discuss representation of drug exposure in pharmacoepidemiological investigations of the connection between diabetes drugs and cancer risk. We identify principles that might improve future research (particularly in observational studies), and consider issues related to reverse causation and detection bias (The Lancet Diabetes & Endocrinology)
Linagliptin lowers albuminuria in T2D & renal dysfunction
Linagliptin administered in addition to stable RAAS inhibitors led to a significant reduction in albuminuria in patients with type 2 diabetes and renal dysfunction. This observation was independent of changes in glucose level or SBP (Diabetes Care)
Prescribing for Diabetes,England 2005-06 to 2012-13
The prescribing data covers prescriptions written by general practitioners, nurses, pharmacists and others working in primary care (Health and Social Care Information Centre)
Glucose-Responsive Microgels & Nanocapsules for Closed-Loop Insulin
Acting as a self-regulating valve system, microgels were adjusted to release insulin at basal release rates under normoglycemic conditions and at higher rates under hyperglycemic conditions. These microgels with enzyme nanocapsules facilitate insulin release and result in a reduction of blood glucose levels in a mouse model of type 1 diabetes (Nano)
Effects of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Disease T2D
DPP-4 inhibitors have some CV protective effects in T2DM in addition to their antidiabetic actions. Additional benefits include lowering the blood pressure, improving the lipid profile and the endothelial dysfunction, decreasing the macrophage-mediated inflammatory response, and reducing myocardial injury. Further investigation in a large cohort is warranted to assess the exact mechanisms of CV protective effects of DPP-4 inhibitors (Journal of Diabetes Research)
Trends in selection & timing of first-line pharmacotherapy in older T2D
Metformin has become the most commonly used initial medication for the treatment of diabetes. Although guidelines have evolved to recommend more aggressive initiation and intensification of pharmacotherapy, our results suggest that the time from diagnosis to initiation has increased substantially (Diabetic Medicine)
Mechanisms of action of Sitagliptin Used Alone or With Metformin in T2D
M+S combined produce additive effects to 1) reduce FPG and postmeal PG, 2) augment GLP-1 secretion and ß-cell function, 3) decrease plasma glucagon, and 4) inhibit fasting and postmeal EGP compared with M or S monotherapy (Diabetes Care)
Fundamental Role of DPP-4 Inhibitors and GLP-1 Receptor Agonists
Based on an expanding and favorable literature describing their use in various patient populations, the guidelines of the American Association of Clinical Endocrinologists (AACE) and the recently updated guidelines from the American Diabetes Association (ADA) assign these agents a central role in the treatment of T2D (Endocrine Practice)
Safety, tolerability, pharmacokinetics, pharmacodynamics empagliflozin
Oral administration of empagliflozin at doses of 10 mg, 25 mg or 100 mg once daily over 28 days resulted in significant increases in UGE and reductions in blood glucose compared with placebo, and were well tolerated in patients with type 2 diabetes (Diabetes, Obesity and Metabolism)
The Efficacy and Safety of Insulin Degludec
The use of extreme dosing intervals of 8–40 h demonstrates that the daily injection time of IDeg can be varied without compromising glycemic control or safety (Diabetes Care)