Selecting Glucose-Lowering Combinations for Type 2 Diabetes Mellitus – Incretins, SGLT2 Inhibitors and Pioglitazone
DeFronzo RA, presented a session at the American Diabetes Association (ADA) 2021 81st scientific sessions: virtual which covered the three aspects of the sodium-glucose transport protein 2 inhibitors (SGLT2i) i.e. metabolic, cardiovascular and renal. The 2014 JCEM study showed that Dapagliflozin treatment had significant improvement in insulin sensitivity, insulin secretion and β-cell function. SGLT2i corrects a novel pathophysiologic defect, reduces HbA1c and promotes weight loss, complements action of other antidiabetic agents, reverses the glucotoxicity and reduces the blood pressure with no hypoglycemic events, leading to an improvement in glycemic control and cardiovascular risk factors.
The 3 major trials DECLARE, CANVAS, EMPA-REG favours SGLT2i as it significantly reduces MACE composite of CV death, non-fatal MI, non-fatal stroke, hospitalization for heart failure an renal outcome. SGLT2i showed many CV benefits via several mechanisms such as it decreases BP and plasma volume without increase in heart rate. These drugs also markedly reduce arterial stiffness and SNS activity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) effectively reduces HbA1c, preserves β-cell function, promotes weight loss, no hypoglycemia, and reduces CV events with excellent safety profile.
The 4 major trials LEADER, SUSTAIN, EXSCEL, REWIND showed effective results of SGLT2i Liraglutide, Semaglutide, Exenatide and Dulaglutide which significantly reduces MACE with HR of 0.87, 0.74, 0.91 and 0.88, resp. GLP-RAs are anti-atherogenic, anti-inflammatory, anti-oxidative stress, anti-thrombotic and showed direct myocardial effect, causes weight loss, decreased postprandial lipemia and BP. All the major trials LEADER, SUSTAIN, EXSCEL, REWIND showed beneficial effect of GLP-RAs on renal outcome including macroalbuminuria. Pioglitazone significantly reduces CV events such as time to death, MI or stroke in PROACTIVE study and also in meta-analysis of clinical trials. In IRIS study, Pioglitazone significantly improves patient survival in MI and stroke patients. In T2DM patients, Pioglitazone halts progression of carotid IMT and coronary atherosclerosis.
The combination therapy of SGLT2i and GLP-1RAs, SGLT2i and Pioglitazone and GLP-1RAs and Pioglitazone showed additive benefits in cardiovascular and renal outcomes.
Telehealth in Ocular Care for Diabetic Retinopathy before and after COVID-19
Modjtahedi BS, presented a session at the American Diabetes Association (ADA) 2021 81st scientific sessions: virtual congress. Even though diabetic retinopathy causes significant visual morbidity on a population-based level, it only affects a minority of diabetic patients. There is need to reach a large population with wide scale screening in a cost-effective and efficient manner.
Diabetes care at Kaiser Permanente Southern California (KPSC) incorporated 47,000 diabetic patients. Patient used to be screened either in clinic or through a telemedicine program staffed by ophthalmologist. It was reported that transitioned to a centralized reading center leads to detection of diabetic retinopathy improved from 10.1% to 22.6%. Two year incidence of retinal intervention in patients with minimal or no diabetic retinopathy on telemedicine screening reported that it is rare for patients with minimal or no baseline retinopathy to require retinal interventions in the 2 years after retinal evaluation. It appears that extending the recommended follow-up interval for low-risk patients may be appropriate as long as this does not lead to worse follow-up in later years, since most are unlikely to have vision-threatening disease that requires treatment.
Eye monitoring benefits includes remove the extra MD visit to reduce points of contact with patients, high quality care, higher coordination of testing, and efficient and cost effective. Health system factors include phone calls, emails and text messages reminders were extremely important. Negative factors include inconvenient available appointment times, processes used to schedule appointments, and cancellations or rescheduling of appointments by offices. So there is need to implement solutions such as increasing multi-lingual outreach, coordinating patient movement with primary care offices and offering after hours and weekend visits for screening/monitoring.
Using the COVID-19 pandemic as an opportunity to re-engineer care there is need to build new tele-health models which helps to reduce patient time spent in healthcare settings, develop predictive modeling to better triage patients by leveraging retinopathy status, demographic information, and laboratory data, and improve outreach for those patients who are lost to follow-up.
Professional Interest Group Discussion on Diabetes in Youth—Identification and Management of Prediabetes in Youth— Pros vs. Cons
Lawrence JM, et.al. conducted a session on Professional Interest Group Discussion on Diabetes in Youth—Identification and Management of Prediabetes in Youth— Pros vs. Cons on Sunday June 27th, 2021 at American Diabetes Association (ADA) 81st Scientific Sessions, a Virtual Experience.
Silva Arslanian presented study findings for Identification and Management of Prediabetes in youth; its pros and cons. She mentioned about beta cell function in Type 2 Diabetes (T2D) in obese youth. Insulin sensitivity and insulin secretion in prediabetic youth was also discussed. In order to diagnose prediabetes in youth, certain parameters such as management, definitions and pros and cons were also discussed. Tamara S Hannon presented top 10 reasons to promote the identification and treatment of prediabetes in youth. The same were: Diabetes is a devastating public health problem, a spectrum, declining beta cell function is found to be evident in in impaired glucose tolerance (IGT), complications of diabetes are evident in IGT, and T2D goes undetected and untreated. The other problems are: youth have rapid progression of diabetes, treatment of IGT was found to be associated with stable measures of glycemia and clinical follow-up is important to recognize and treat diabetes expediently and it’s important to measure and treat.
In the RISE study, kids with IGT or recently diagnosed T2D in past 6 month with good glycemic control were enrolled. The study population was either treated with Glargine/ Metformin titrated to a fasting glucose for 3 months or Metformin for 12 months. Fasting glucose remained same in both groups. In same group, 2 hr. glucose did not worsen in either group after 15 months therapy. Clinical follow-up of youth with obesity and prediabetes is important. Policies for prevention of diabetes are to be promoted and IGT and T2D are to be identified earlier treated expediently. Phil Zeitler presented 10 reasons against the diagnosis and treatment of prediabetes in youth. The author mentioned that prediabetes definition in youth is yet unknown while criteria for diabetes in have never been validated in youth. Prediction of progression of diabetes in youth is yet unclear.
The authors discussed the pros and cons of managing prediabetes in youth by highlighting various reasons and studies.
Therapeutic Development in Patients with Diabetes – Target or Outcome? A Cardiologist’s Perspective
Bonaca MP gave an oral presentation on “Therapeutic Development in Patients with Diabetes—Target or Outcome? A Cardiologist’s Perspective” at the American Diabetes Association (ADA) 81st Virtual Scientific Session. One perspective offers that FDA has a critical responsibility for evaluating drug safety and efficacy. The bar is already very high and requires a significant investment of resources, time and patient volunteers. But a label is what is needed. For patients to benefit, a drug also needs a compelling story for payers, a compelling story for clinicians, a compelling story for benefits/risks and tolerability for patients (most important) and some may prioritize the quality of life.
The other perspective offers that there are vascular beds outside the coronaries and that they matter. There is heterogeneity of risk and response to therapy in ASCVD. Driving utilization in these disease states will depend on data from dedicated trials that rigorously evaluate the endpoints that matter for different ASCVD populations.
Therapies to prevent macrovascular complications in patients with cardiovascular disease and diabetes are a very crowded space. Glucose lowering is beneficial for microvascular diseases but newer agents developed for this purpose alone will need to be extremely safe, well-tolerated and cost-effective relative to existing therapies (metformin -GLP1a and SGLT2i- DPP4- TZD- a fifth or sixth drug?)
Regardless of the regulatory requirements, novel therapies need to tell a compelling risk. Benefit story that can be personalized to individual patients in the cardiovascular clinic.
ADA Presidents’ Select Abstract: Potential Gains in Life Expectancy (LE) Associated with Achieving Treatment Goals in People with Type 2 Diabetes (T2D) in the U.S
A study by Hamed Kianmehr was presented on Sunday, June 27, 2021 at American Diabetes Association (ADA) 81st Scientific Sessions, a Virtual Experience. The objective of this study was to evaluate the co–relation between fulfilment of treatment goals and prolonged life in type 2 diabetes patients.
In light of the same, the BRAVO diabetes microsimulation model that was previously developed and validated was calibrated to a US representative cohort and this model was then used to project life expectancy by level of A1c, systolic blood pressure, low density lipoproteins and body mass index.
According to the results, it was found that a decrease in body mass index was associated with the largest gain in life expectancy which was in turn followed by lowering of systolic blood pressure and low-density lipoproteins. A decrease in A1c from 9.1% to 7.2% quartile was equated with a gain of about 2 years but any further reduction in A1c was associated with negligible gains in life expectancy.
These findings can act as a guide for clinicians in encouraging patients to achieve the suggested treatment goals. Additionally, it can also play a role in evaluating potential health benefits for programs to improve diabetes care.
Selecting Intervention Population for Lifestyle Program for Type 2 Diabetes Prevention (LPT2DP): A Cost-Effectiveness Perspective
A study by Joohyun Park was presented on Sunday, June 27, 2021 at American Diabetes Association (ADA) 81st Scientific Sessions, a Virtual Experience. The objective of the study was to determine the cost – effectiveness of lifestyle program for Type 2 diabetes prevention.
The study started off by classifying the current lifestyle program for type 2 diabetes prevention into three major types that is delivered in person individually, in group or delivered virtually. The CDC – RTI cost effectiveness simulation model was used to measure the cost – effectiveness of the three types of lifestyle programs for type 2 diabetes.
This was carried out in eleven population groups wherein the annual incidence of developing type 2 diabetes mellitus ranged from 1% to 11%. $50K and $20K per quality-adjusted life year (QALY) gained in 25-years was used to measure the cost – effectiveness of the lifestyle program for type 2 diabetes prevention.
Based on the analysis of the results, it was found that, when $50K/QALY was used, the annual type 2 diabetes incidence of the target population needed to be more than or equal to 5% for the individual program, 4% for the digitally made available program and 3% for the in – person group program. Subsequently when $20K/QALY was being used, the type 2 diabetes risk thresholds were greater for each program.
This study can thus be of assistance when it comes to picking out the most appropriate population for a lifestyle program for type 2 diabetes prevention.
Health Care Coverage and Access and Associations with Glycemic Control in Young Adults with Youth-Onset Diabetes: The SEARCH for Diabetes in Youth and TODAY Studies
A study by Catherine Pihoker was presented on Sunday, June 27, 2021 at American Diabetes Association (ADA) 81st Scientific Sessions, a Virtual Experience. The purpose of this study was to investigate healthcare coverage and access to care and its association with HbA1c by diabetes type.
The study comprised of a total of 1374 participants with a mean age of 25 years who completed the interviewer – administered surveys on health – care coverage. Following which, the co – relation between healthcare coverage and access and HbA1c were evaluated separately in type 1 and type 2 diabetes.
Based on the analysis, it was found out that the mean HbA1c values were similar for both types of diabetes for those who possessed public insurance, but a spike was observed in type 1 diabetes patients with no insurance. A strong association was found between having health insurance and a place for diabetes care with low HbA1c levels in case of type 1 diabetes patients but this trend was not observed in type 2 diabetes patients. Participants belonging to states possessing Medicaid eligibility expansion were more prone to have health insurance for type 1 as well as type 2 diabetes.
Thus, healthcare coverage and access appeared to have a strong co-relation with better glycemic control in young adults with type 1 diabetes but the same cannot be said for participants with type 2 diabetes. A thorough understanding of the distinct role healthcare access factors play in both, type 1 and type 2 diabetes is essential.
A New Type 2 Diabetes Microsimulation Model to Estimate Long-Term Health Outcomes, Costs, and Cost-Effectiveness
A model-based study by Thomas J Hoerger was presented on Sunday, June 27, 2021 at American Diabetes Association (ADA) 81st Scientific Sessions, a Virtual Experience. The idea behind development of the microsimulation model was to be able to estimate the health effects, costs, and cost-effectiveness of public health interventions for type 2 diabetes.
The model integrated the risk equations for complication and mortality, risk factor progression and patient utility. Additionally, the model also possessed a web – based interface that allowed the user to switch up the parameters. It included interventions for glycemic, blood pressure, cholesterol control, smoking cessation and a generic intervention that users could modulate.
In order to display the way by which the model estimated cost – effectiveness, an intervention to reduce HbA1c from 9% to 7% was analysed. The study comprised of a cohort of 10,000 individuals with type 2 diabetes and long – run health effects, costs and quality adjusted life years were estimated.
Based on the analysis, it was found out that the patients had 20.16 remaining life years (from a mean age of 61), they were to incur around $187,435 in discounted medical costs and were also set to experience 8.89 discounted QALY’s. Greatest sensitivity of the results was observed to the age and duration of diabetes at baseline.
The intervention to reduce HbA1c produced $3,151 in incremental costs and gained 0.4 QALYs, producing an incremental cost-effectiveness ratio of $7,838 per QALY. While the model appeared to perform well in internal validation exercises, in the external validation exercises, it seemed to be better at predicting results of clinical trials.
Thus, as the model’s risk progression, patient utility, and costs are all derived using recent U.S. studies, it can play a crucial role in accurately estimating the long-run health impact, costs, and cost-effectiveness of interventions for type 2 diabetes.
Increased Adiposity and Low Height-for-Age in Early Childhood Is Associated with Later Metabolic Risk in American Indian Children and Adolescents
A study by Maria J Ramirez-Luzuriaga was presented on Sunday, June 27, 2021 at American Diabetes Association (ADA) 81st Scientific Sessions, a Virtual Experience. The objective of this study was to evaluate the effect of growth abnormalities in early childhood to subsequent metabolic risk.
The study comprised of 701 participants belonging to the age group of 5 – 16 years. Age and sex-specific z-scores of weight-for-height (WHZ) and height-for-age (HAZ) of children less than five years old were found out. Having selected the highest observed WHZ and the lowest HAZ, an analysis of associations of categories of WHZ and HAZ with metabolic data at ages 5-9 and 10-16 was carried out.
Based on the analysis, it was found out that the characteristic of being overweight and obese (WHZ > 2) in children less than 5 years had an association with higher BMI and greater height at ages 5-16 relative to normal weight (WHZ ≤ 1). Additionally, it was also associated with increased fasting glucose, 2-h glucose, fasting insulin, 2-hr insulin, total cholesterol, triglycerides, SBP, DPB and decreased HDL.
Low height-for-age (HAZ< -2) in children below five years of age was associated with lower BMI and lower height at ages 5-16 relative to the normal height (HAZ ≥ 0). The low height-for-age was associated with 1.40 times higher 2-h insulin and 5.47 mg/dL lower HDL.
Thus, these findings pinpoint towards the fact that, both overweight/obesity and low height-for-age in early childhood can impact subsequent metabolic risk in American Indian children and adolescents.
Food Insecurity and Glycemic Control among Youth and Young Adults with Type 2 Diabetes
A study by Lauren A Reid was presented on Sunday, June 27, 2021 at American Diabetes Association (ADA) 81st Scientific Sessions, a Virtual Experience. The objective of this study was to evaluate the association between household food insecurity and glycemic control in youth and young adults with Type 2 diabetes.
A cross- sectional study was carried out and the study comprised of 395 youth and young adults with Type 2 diabetes. HbA1c values were measured in a sample of whole blood and analysed as a continuous variable. The glycemic control was divided into optimal/suboptimal (≤9 %) vs. high risk (> 9.0%) based on the HbA1c values.
Based on the analysis, it was found out that, around 34% of youth and young adults with Type 2 diabetes reported household food insecurity in the past 12 months. The mean HbA1c of the youth and young adults with household food insecurity was 9.2%. Around 54% had HbA1c >9.0% and 19% reported experiencing diabetic ketoacidosis or hypoglycemia.
Youth and young adults who were food secure had a mean HbA1c of 9.5%. Additionally, 54% had HbA1c >9.0% and 8% reported acute complications. No association was observed between household food insecurity and HbA1c or glycemic control. Youth and young adults with household food insecurity had 2.3 times the odds of encountering diabetic ketoacidosis or hypoglycemia as those without household food insecurity.
Thus, based on these findings, it was concluded that household food insecurities amongst youth and young adults with type 2 diabetes is a common occurrence and it is further associated with acute diabetes-related complications.
