- Evenement
- Bron: Campus Sanofi
- 10 okt 2023
American Diabetes Association: 83rd Scientific Sessions
The Therapeutic Education Corner
The Incretin Corner
SURMOUNT-2 Trial Results and Potential Role of Tirzepatide in Treating Obesity in Type 2 Diabetes3
The New Normal Corner
A 360-Degree Examination of Type 1 Diabetes: From Patient Identification to Treatment and Prevention
The Therapeutic Education Corner
The Incretin Corner
SURMOUNT-2 Trial Results and Potential Role of Tirzepatide in Treating Obesity in Type 2 Diabetes3
The New Normal Corner
A 360-Degree Examination of Type 1 Diabetes: From Patient Identification to Treatment and Prevention
The Therapeutic Education Corner
Overcoming Therapeutic Inertia—Leveraging the Diabetes Care Interprofessional Team
This symposium was chaired by Nuha Ali El Sayed and featured a presentation by Kevin Pantalone in which he discussed the definition, key contributors, challenges and best practices to overcome TI in T2D. He highlighted that people with T2D (PwT2D) must follow “Treat To Target” approach instead of historical “Treat To Failure” approach for effective diabetes management. Further, he emphasized the importance of leveraging the diabetes care team to identify as many as touchpoints with our patients to overcome TI in PwT2D.
During the presentation, the panelists (Kevin Pantalone, Sandra Leal and Lucia Novak) discussed diverse case studies and best practices to tackle TI with the use of technology (telehealth, continuous glucose monitoring, coaching programs etc.), dedicated endocrine pharmacists and schedule follow-up visits of patients with clinicians to achieve recommended glycemic targets.
Fig. 1: Word cloud representation of feedback from the 2018 therapeutic inertia summit. Participants were asked to list the top three words that describe potential solutions to therapeutic inertia. The size of the words indicates the relative frequency with which they were mentioned2.
The Incretin Corner
SURMOUNT-2 Trial Results and Potential Role of Tirzepatide in Treating Obesity in Type 2 Diabetes
The SURMOUNT-2 trial was a 72-week, randomized, multicenter, double-blind study, designed to assess the safety and efficacy of Tirzepatide 10 mg and 15 mg, and placebo for chronic weight management in PwT2D with obesity.
In the SURMOUNT-2 study, both Tirzepatide 10 mg and 15 mg doses demonstrated superiority and clinically meaningful body weight reduction versus placebo (primary endpoint). Moreover, the tolerability and safety profile of Tirzepatide in PwT2D with obesity was consistent with the SURPASS studies results and that of other incretin-based therapies for obesity. The most frequent AE reported were GI-related (mild-moderate) and no severe hypoglycemia was reported.
However, some critical outstanding questions from the SURMOUNT-2 study include durability beyond 1.5 years, cardiac and renal outcomes, early use in younger patients, RWE data and healthcare savings with Tirzepatide.
The results of this study are now published in The Lancet journal.
Fig.2: Effect of once weekly tirzepatide, compared with placebo, on HbA1c and bodyweight. (A) HbA1c values over time from MMRM analysis for the efficacy estimand and week 72 estimates from ANCOVA for the treatment-regimen estimand. (B) Percent change in bodyweight over time from baseline to 72 weeks, derived from a mixed-model for repeated-measures analysis for the efficacy estimand; week 72 estimates for the treatment-regimen estimand are also shown.
The Basic Science Corner
The Jekyll and Hyde of Inflammatory Signals in Islets
On the last day of the congress, Daniël van Raalte presented the role of gut microbiota in diabetes. Evidence shows that low-grade beta-cell inflammation has been identified in type 2 diabetes (T2D). On the other hand, “Gut dysbiosis” has been proposed in people with T2D. Therefore, microbiota may participate to the induction of islet cell inflammation and dysfunction. However, causality has yet to be proven.4
Regarding T1D, the role of microbiota is clearer in autoimmune development and fecal transplant is being proposed for potential therapy for T1D; clinical trials in Vancouver, Canada are underway.5
Fig 3.: Study schematic showing which analyses were performed (left). Left graph: Change in fasting C peptide over time. Arrows indicate when FMT (allogenic: blue and autologous: pink with width of colour band indicating SD) was performed. Ribbons indicate CIs. Significance was calculated using LMM, *** p=0.00019. Right graph: Change in C peptide AUC over time. Significance was calculated using LMM, **** p=0.000067. AUC, area under the curve; FMT, faecal microbiota transplantation; LMM, linear mixed model; T1D, type 1 diabetes.
The ADA Corner
Updates in ADA’s Standards of Care in Diabetes—2023
This symposium was chaired by Dr. Nuha Ali El Sayed and Dr. Raveendhara Bannuru and featured presentations by Dr. Vanita Aroda, Dr. Dennis Bruemmer, Dr. Eric Johnson, Dr. Grazia Aleppo, Dr. Kenneth Cusi and Dr. Adham Abdel Mottalib on updates in ADA-2023 standards of care in diabetes.
Key points highlighted during this session included:
- Dr. El Sayed, and Dr. Bannuru opened the session by providing an overview of methodology used in developing and updating Standard of Care (SOC) with 2 key updates being made in section 3 of SOC with respect to prevention and delay of T1D and T2D with inclusion of the recently approved teplizumab to delay the onset of T1D and in section 4 in SOC with respect to NAFLD (nonalcoholic fatty liver disease).
- Dr. Aroda, presented information on heterogenous progression of pre-diabetes to T2D, where elderly individuals had less progression compared to younger and more obese cohort from pre-diabetes to T2D which can be attributed to different phenotypes (ARIC study).
- The updates to ADA’s SOC in section 3.2 are use of more precise language to identify higher risk for diabetes (e.g., BMI>35, higher glycemic indices). Further, the pre-diabetes pharmacotherapy should include weight loss and decrease CV risk and inclusion of pioglitazone after stroke or TIA (IRIS study) in PwD.
- Dr. Bruemmer discussed findings from key trials on BP and lipids (ACCORD, SPRINT, STEP, Heart Protection Study) and refresher on goals of therapy which included BP < 130/80, lipid levels and use of high intensity statins.
- The review on secondary prevention was showcased with role of PCSK9 inhibitors and corresponding studies (ODYSSEY_ Lipoprotein(a) lowering by alirocumab reduces the total burden of cardiovascular events independent of low-density lipoprotein cholesterol lowering: ODYSSEY OUTCOMES trial | European Heart Journal | Oxford Academic (oup.com)) and ezetimibe with mention of AACE and ESC goal (LDL <55). The discussion further added information on diabetes medication with the role of GLP-1s and SGLT-2s and its cardiorenal effects.
- Dr. Johnson informed the audience about the role and importance of Community Health Care Workers and use of person-centered language example use of term “Person with diabetes” or “PwD” instead of “diabetic”.
The New Normal Corner
A 360-Degree Examination of Type 1 Diabetes: From Patient Identification to Treatment and Prevention
Numerous sessions addressed screening and immunotherapy for T1D.
In a joint ADA/JDRF symposium chaired by Sanjoy Dutta, Anette-Gabriele Ziegler, Cristy Geno Rasmussen and Riita Veijola discussed diabetes screening and monitoring perspectives from Germany, the USA and Northern Europe.
Key points highlighted during this session included:
- To optimize sensitivity and positive predictive value for detecting T1D during childhood and adolescence, the optimal ages to screen for T1D are 2, 6, and 10 years. Indeed, screening at ages 2 and 6 years results in 82% sensitivity7.
- Due to variability in testing methods, post-infusion monitoring needs to be individualized. Autoimmunity Screening for Kids (ASK) study mentions that A1C is a specific but not sensitive indicator for diagnosis of early T1D, especially in children8.
- DiaUnion in Sweden and Denmark initiated screening for islet autoimmunity in the general childhood population (DiaUnion – Research in Diabetes and Autoimmunity).
In another panel discussion chaired by Dr. Ellen W Leschek, the panelists presented their perspectives on the use of immunotherapies from various settings.
Key points highlighted during this session:
Dr. Leschek presented a brief overview of the TN-10 study9 and discussed future needs focusing on pediatric indications and looking at combination therapies. She also discussed barriers including operational and cost.
Dr. Herold provided an update on the TN-10 trial10 showing that participants continue to show a 52 months delay versus 27 months delay in the placebo group. Dr. Herold mentioned that there is a transient reduction in the number of circulating T-cells, but the cell number was back to baseline values after 6 weeks of treatment. He also highlighted that people with a high proinsulin to C-peptide ratio were likely to progress to stage 3 T1D faster than those with a lower ratio. However, these participants showed a more robust response to teplizumab.
Referenties
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American Diabetes Association. Summary of Proceedings of the American Diabetes Association Summit “Overcoming Therapeutic Inertia: Accelerating Diabetes Care FOR_LIFE.” Arlington, VA, American Diabetes Association, 2019
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Gabbay RA, Kendall D, Beebe C, et al. Addressing Therapeutic Inertia in 2020 and Beyond: A 3-Year Initiative of the American Diabetes Association. Clin Diabetes. 2020;38(4):371-381. doi:10.2337/cd20-0053
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Garvey WT, Frias JP, Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial [published online ahead of print, 2023 Jun 26]. Lancet. 2023;S0140-6736(23)01200-X. doi:10.1016/S0140-6736(23)01200-X
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Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490(7418):55-60. doi:10.1038/nature11450
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de Groot P, Nikolic T, Pellegrini S, et al. Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial. Gut. 2021;70(1):92-105. doi:10.1136/gutjnl-2020-322630
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ElSayed NA, Aleppo G, Aroda VR, et al. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023 [published correction appears in Diabetes Care. 2023 Feb 01;:]. Diabetes Care. 2023;46(Suppl 1):S19-S40. doi:10.2337/dc23-S002
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Ghalwash M, Dunne JL, Lundgren M, et al. Two-age islet-autoantibody screening for childhood type 1 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol. 2022;10(8):589-596. doi:10.1016/S2213-8587(22)00141-3
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Steck AK, Dong F, Geno Rasmussen C, et al. CGM Metrics Predict Imminent Progression to Type 1 Diabetes: Autoimmunity Screening for Kids (ASK) Study. Diabetes Care. 2022;45(2):365-371. doi:10.2337/dc21-0602
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Herold KC, Bundy BN, Long SA, et al. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes [published correction appears in N Engl J Med. 2020 Feb 6;382(6):586]. N Engl J Med. 2019;381(7):603-613. doi:10.1056/NEJMoa1902226
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Sims EK, Cuthbertson D, Herold KC, Sosenko JM. The Deterrence of Rapid Metabolic Decline Within 3 Months After Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes. Diabetes. 2021;70(12):2922-2931. doi:10.2337/db21-0519