Societal value and health economic benefits of GLP‐1 drugs in the United States

Health economics of allergen-specific immunotherapy in the United States

Diabetes mellitus, defined as a fasting plasma glucose of ≥126 mg/dL or a glycosylated hemoglobin A1c level (HbA1c) of ≥6.5%, afflicts ≈12.9% of adults in the United States and nearly 285 million adults worldwide.1,2 Diabetes mellitus is a major risk factor for the development of cardiovascular disease, independently conferring a 2-fold excess risk of coronary heart disease and stroke.3 Macrovascular events in diabetes mellitus remain the leading cause of mortality, and the burden of cardiovascular disease attributable to diabetes mellitus has increased over the past decade.4 An increase in the prevalence of obesity has contributed to the rise in diabetes mellitus. Additionally, obesity independently increases the risk of cardiovascular disease in patients with diabetes mellitus.5 Although strict glycemic control unequivocally reduces the microvascular complications of diabetes mellitus, the macrovascular benefits of intensive therapy have been difficult to establish, with conflicting results from large clinical trials.6–9 Multifactorial strategies are recommended to reduce cardiovascular risk in diabetes mellitus through enhanced glycemic control, blood pressure reduction, lipid management, weight loss, and physical activity.10 Unfortunately, despite aggressive interventions for hyperglycemia, <50% of patients achieve standard HbA1c targets with conventional therapy.11 Polypharmacy is required to achieve glycemic control in the majority of patients within 3 years of diagnosis.12 Although combinations of drug classes can synergistically target multiple pathophysiological defects, novel therapies are required to manage diabetes mellitus and mitigate cardiovascular risks. Dipeptidyl-peptidase IV (DPP-IV) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist incretin therapies were developed to complement conventional treatment options for diabetes mellitus. Despite promising initial reports of cardioprotective effects, DPP-IV inhibitors have failed to demonstrate improved cardiovascular outcomes in large clinical trials.13–15 Randomized studies to evaluate cardiovascular outcomes associated with GLP-1 receptor agonists are currently underway. This review presents …

Cost or price of sequencing? Implications for economic evaluations in genomic medicine

New Medications for the Treatment of Diabetes.

An Albumin-Exendin-4 Conjugate Engages Central and Peripheral Circuits Regulating Murine Energy and Glucose Homeostasis

Preoperative considerations of new long-acting glucagon-like peptide-1 receptor agonists in diabetes mellitus

ObjectiveTo examine longitudinal changes in the initial prescribing of glucagon‐like peptide 1 (GLP‐1) receptor agonists for women of reproductive age in Australia; to determine whether contraception recommendations are being followed; and to estimate the frequency of pregnancy among women using GLP‐1 receptor agonists.Study designRetrospective open cohort study; analysis of MedicineInsight general practice data.Setting, participantsWomen aged 18–49 years who visited participating general practices three or more times during the study period (1 January 2011 – 31 July 2022).Main outcome measuresAge‐standardised incidence of initial GLP‐1 receptor agonist prescribing, by year and type 2 diabetes status; proportion of women using highly effective contraception at the time of GLP‐1 receptor agonist initiation (contraception overlap); age‐standardised incidence of pregnancy within six months of the first prescribing of GLP‐1 receptor agonists.ResultsOf 1 635 684 women aged 18–49 years, 18 010 (1.1%) were first prescribed GLP‐1 receptor agonists during 2011–2022, of whom 3739 (20.8%) had type 2 diabetes. The age‐standardised incidence of GLP‐1 receptor agonist prescribing for women with type 2 diabetes increased from 13.0 per 1000 women in 2011 to 88.5 per 1000 women in 2022; for women without type 2 diabetes, it increased from 0 to 14.9 per 1000 women. Of the 6293 women first prescribed GLP‐1 receptor agonists during 2022, 6954 (90.5%) did not have type 2 diabetes. Contraception overlap with first prescribing of GLP‐1 receptor agonists was determined for 3825 women (21.2%). Pregnancies within six months of GLP‐1 receptor agonist prescribing were documented for 232 of 10 781 women for whom at least six months of follow‐up data were available.ConclusionsThe prescribing of GLP‐1 receptor agonists for women of reproductive age is increasing in Australia, and most prescriptions are for women not diagnosed with type 2 diabetes. Fewer than one in four women are using contraception at the time of treatment initiation, and a considerable number are pregnant within six months of the initial prescribing of GLP‐1 receptor agonists. Further evidence and guidelines are needed to support the safe and effective use of GLP‐1 receptor agonists by women of reproductive age.

New Glucose-Lowering Agents for Diabetic Kidney Disease.

New Medications for the Treatment of Diabetes

Paying the Price for Eating Ice Cream: Is Excessive GLP-1 Signaling in the Brain the Culprit?

Current and emerging medications for the management of obesity in adults.

Is There a Starling Curve for Intensive Care?

ABSTRACTBones have been suggested to be a target for glucagon‐like peptide ‐1 (GLP‐1); however, studies of the effects on human bones so far have given diverging results. We hypothesized that GLP‐1, together with glucagon‐like peptide‐2 and glucose‐dependent insulinotropic polypeptide, plays a role in the gut–bone axis. We examined the acute effect of three GLP‐1 receptor ligands [GLP‐1 (7‐36)amide, GLP‐1 (9‐36)amide, and exenatide] on markers of bone remodeling. Eight healthy, normal‐weight participants, with a mean age of 24.3 years, were studied for 4 days in a double‐blinded, randomized clinical trial. Blood was collected before and after s.c. injection of GLP‐1 (7‐36)amide (1.5 nmol/kg), GLP‐1 (9‐36)amide (1.5 nmol/kg), exenatide (2.4 nmol/subject), or saline. Plasma was analyzed for bone markers and for osteoprotegerin (OPG), PTH, and IGF‐1 levels. All ligands were tested in vitro for their cAMP‐inducing activity on the human GLP‐1 receptor. GLP‐1 (7‐36)amide decreased CTX‐levels, compared with placebo (area under the curve [AUC] ±SD 0 to 120 min = –2143 ± 1294 % × min versus –883 ± 1557 % × min; p < 0.05). No difference was observed between placebo and GLP‐1 (9‐36)amide, or between placebo and exenatide, although exenatide had a similar potency as GLP‐1 (7‐36)amide for cAMP formation in vitro (EC50 of 0.093 and 0.054 nmol/L). However, exenatide reached maximum plasma concentration at 90 min versus 15 min for GLP‐1 (7‐36)amide, and plasma CTX was significantly decreased during the second hour of the study after exenatide injections compared with placebo (AUC ±SD –463.1 ± 218 % × min and –136 ± 91 % × min; p < 0.05). There was no effect of the injections on bone formation markers (P1NP and osteocalcin) or on OPG, PTH and IGF‐1 levels. In conclusion, we show that GLP‐1 receptor agonists, but not the primary metabolite GLP‐1 (9‐36)amide, decrease bone resorption, and suggest that GLP‐1 may be part of the gut–bone axis. © 2019 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

COVID-19 Health Economics: Looking Back and Scoping the Future

To the Editor: In their commentary on the ethical aspects of generic and therapeutic substitution, AlAmeri et al. [1] argued that the health economic rationale for promoting substitution, i.e. the creation of cost savings to the health care system, may be harmful to patients and, thus, that substitution is unethical. They then go on to state that the debate on whether or not to substitute must be exclusively informed by the individual patient’s clinical interests and that substitution driven by economic interests is not compatible with patient-centered medicine. In putting these arguments forward, the authors misinterpret the ethical implications of a health economic framework by focusing on the individual patient’s perspective to the detriment of the societal perspective. The ethical dimension underpinning health economics is that a society wishes to maximise population health subject to a budget constraint. This idea is reflected in the term ‘health economics’, which consists of two words, with ‘health’ coming first and ‘economics’ coming second. Given that society can fund some, but not all available health technologies in an era of limited resources, society allocates the finite budget to those health technologies that maximize population health. Health economic theory has demonstrated that, if health technologies are ranked according to their cost-effectiveness, health can be maximised by funding health technologies in decreasing order of cost-effectiveness until the budget is exhausted. In this respect, substitution can increase the cost-effectiveness of existing pharmacotherapy and improve population health, as shown for example by the increasing cost-effectiveness of all statin therapies in Spain following the introduction of generic statins [2]. AlAmeri et al. [1] agreed that if clinical studies have demonstrated an equal safety and effectiveness profile of a generic medicine and the reference medicine, then substitution can be undertaken and the least expensive medicine needs to be chosen. However, it may be ethical to substitute the reference with a generic medicine even if the generic medicine is less effective than the reference medicine. Health economics shows that substitution can be costeffective if the savings in total health care costs are large enough to offset the reduction in effectiveness. If substitution is undertaken in this scenario, society is able to free resources and invest those in more cost-effective health technologies, thereby generating an overall increase in population health, even when this leads to a decrease in the individual patient’s clinical outcomes. Conversely, prescription of the more expensive reference medicine would improve the individual patient’s clinical outcomes, but would be accompanied by a decrease in population health that is larger than the improvement in the patient’s outcomes. In this respect, health economics chooses the clinical interests of society as a whole in order to be ethical rather than those of the individual patient or of a specific patient group. When discussing the impact of substitution on patient’s clinical interests, AlAmeri et al. [1] considered the potential negative impact of substitution on patient satisfaction and on adherence to treatment, but did not take account of the possible positive impact. For instance, substitution may sustain the affordability of health care and may enable a larger number of patients to gain access to health care. In The author holds the EGA chair ‘European policy towards generic medicines’.