[ Diabetes Type 2 ]

Interpreting Adverse Signals in Diabetes Drug Development Programs

Following on from the success of the inaugural Mapping the management of type 2 diabetes event in 2015, we are delighted to invite you to a second meeting that is again designed to provide practical pointers for the primary care professional on the therapeutic decisions you make for your patients with type 2 diabetes, ensuring that treatment strategies are informed by current guidelines and take account of common comorbidities. The Office of Disease Prevention and Health Promotion (ODPHP) has partnered with the Centers for Disease Control and Prevention (CDC) to offer free continuing education for this eLearning course. We’re beginning to learn about genetic causes of diabetes, but for the majority of people in the United States who have diabetes, the disease is related to behavior that can be changed through lifestyle changes. The benefit was stronger and significant among participants with diabetes but absent in those without diabetes. The emergence of continuous glucose monitoring (CGM) followed in the 1990s, with the first reports on CGM by microdialysis in 1992 (5,6). The purpose of these presentations is to increase awareness of risk factors, signs, symptoms and complications of diabetes, and encourage participants to work with their health care team to prevent or manage diabetes with a healthy lifestyle. The course will be facilitated by Certifies Diabetes Educators.

Your involvement as an American Diabetes Association volunteer — whether on a local or national level — will help us expand our community outreach and impact, inspire healthy living, intensify our advocacy efforts, raise critical dollars to fund our mission, and uphold our reputation as the moving force and trusted leader in the diabetes community. This one-day diabetes training is appropriate for clinical research, medical information, regulatory affairs, biometrics and strategic marketing personnel. They manage Ruben via MDI (Multiple Daily Injections) for 4 1/2 years and then when he was 7 yrs old they moved onto a pump. Educational displays and literature will be set up in high-traffic indoor and outdoor public venues. This review examines the interpretation of adverse signals associated with recently approved blood glucose–lowering agents. The journey from molecule to medicine is likely to take at least 10 years for a new class of agent and to cost ∼$500 million (1–3). If the many unsuccessful drug discovery studies and early development programs are factored in, the average approved drug probably reflects $1.3–1.8 billion of investment, so there is a strong incentive to secure marketing authorization once an agent has progressed through phase 3 (2,3).

Mobile phones are ubiquitous, so there are a number of interventions that are being developed on mobile phones. This review discusses the epidemiologic evidence and animal and human studies supporting the role of these metals in the development of diabetes and ischemic heart disease and potential ways by which EDTA chelation could confer cardiovascular benefit. The adolescents were the most infrequent users of CGM devices. New types of glucose-lowering agents are particularly required for type 2 diabetes because of the multivariable mix of genetic and environmental factors that conspire to create a progressive and highly heterogeneous natural history, with at least eight major organ systems being etiopathogenically implicated (11). With regard to benefit, it is unlikely that an agent will be submitted for marketing authorization if it does not meet recognized approvable efficacy criteria. The generally accepted efficacy surrogate is a reduction in HbA1c that is commensurate with the baseline HbA1c of the patient population studied (greater improvements of glycemic control expected if higher baseline hyperglycemia), taking into account the concomitant health issues within that population and additional benefits of the agent (12). The favorable–unfavorable boundary of benefits and risks will reflect whether efficacy is comparable with or better than existing therapies, achieved by a new mode of action that can be substituted for or add compatibly to these therapies, or assist subpopulations and comorbid conditions inadequately served by existing therapies.

She has published an article in the global diabetes magazine ‘Diabetes Voice’ and several in the Diabetes NZ and Diabetes Auckland issues. Beyond this, theoretical adverse effects might be contemplated with regard to mode of action or other known pharmacodynamic or pharmacokinetic properties (4,5,12). Preregistration trials are mostly designed and powered for a primary efficacy end point, customarily a reduction in HbA1c over 6 months at two or more dosage strengths (Table 3). As durability of efficacy receives more attention, extended randomized controlled trials are envisioned, with greater use of add-on rescue therapy to enable prolonged double blinding, and greater acceptance of post hoc analyses may be required. However, there will always be a desire for more drug exposure to assess risk, especially that pertaining to more vulnerable subpopulations. Dr. Relative risk against a placebo or comparator (or sometimes compared with a separate study of similarly disposed patients) provides a convenient indicator for interpreting frequency and severity of adverse signals, but absolute risk is perhaps more likely to interest the patient and prescriber.

If CGM does not have the desired effect after 3 months, it should be discontinued. This perspective hopefully will rationalize the inevitable limitations of a preregistration trial database as a first step for ongoing surveillance to identify uncommon, rare, or slowly emerging adverse properties, including long-term risks of fatal, life-threatening, or permanently disabling events (13). Tolerability and quality of life may not be strictly within the remit of safety, but they are issues that affect adherence and impinge on benefit-risk deliberations. Risk of diabetes complications and adverse events associated with diabetes drug therapies expressed as absolute risk per 1,000 patient-years. Black bars show representative values for risk in diabetic patients, and gray bars indicate excess risk of events in patients treated with specific glucose-lowering medications relative to diabetic patients receiving comparator therapies. Renata Porter- Immediate Past President Renata has been on the Diabetes Youth New Zealand committee for 5 years. Adapted with permission from Bergenstal et al.

(13). Data were derived from references 13–28. ACCORD, Action to Control Cardiovascular Risk in Diabetes; CHF, congestive heart failure; PVD, peripheral vascular disease; UKPDS, U.K. Prospective Diabetes Study. Because diabetes is for life, comorbid conditions are rife, and therapies mostly last for much longer than the trial periods, the rigorous safety cautions for a new drug approval often require a comprehensive postmarketing risk management program to accompany standard pharmacovigilance monitoring (5). received research grants from Abbott Diabetes Care and Medtronic. Accepting a caveat for the unpredictable, black box warnings can serve a valuable precautionary role to minimize misuse.

Treatment with antidiabetic drugs commonly produces mild hypoglycemic symptoms, especially with insulin, sulfonylureas, or combinations involving these classes (29). Signs of moderate or severe hypoglycemia and extra risks associated with patient unawareness or use in vulnerable groups, such as the elderly or renally impaired, are well rehearsed in product labeling and education packages. Nevertheless propensity for hypoglycemia forms an integral part of the calculation of acceptable risk for all diabetes pharmacotherapies (12). Where clinically significant risk is anticipated with combination therapy, this is typically minimized by recommending down-titration of the existing agent to coincide with the addition of the new agent. The interpretation of hypoglycemic events is usefully assisted by mode-of-action studies, particularly for agents that raise in-sulin concentration, to check whether the already-impaired counterregulatory capability in diabetic hypoglycemic states is further compromised (30).

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