Management Of Hyperglycemia In Type Research Articles

THU250 Therapeutic Inertia In Primary Care With Poor Information Transfer To Specialist Care - A Rural Irish Experience

Abstract Disclosure: C.T. Coughlan: None. T.M. O'Sullivan: None. M.C. O'Donovan: None. M.J. Hannon: None. The burden of diabetes management in Ireland is shared between primary care physicans and specialists in secondary care, using current international management guidelines (1). However, long waiting lists and resource constraints limit the ability of secondary care to respond rapidly to all referrals. This study was designed to identify missed opportunities for early intervention in the management of diabetes in primary care. Written referrals of diabetes patients from primary care physicians to a specialist endocrinology service in a rural Irish hospital were audited to assess both the appropriateness of the referrals and to identify any missed opportunities for starting adjunctive treatments in primary care. We analysed all 74 referrals - mean age 58, 45% female – that were on the hospital diabetes clinic waiting list at the time of data collection. 61/74 (82%) had type 2 diabetes. The average time between date of referral and date of data collection was 231 days. Only 43/74 (58%) included a HbA1c value in the referral document. Of the type 2 diabetes referrals, only 12/61 (20%) included a BMI value. Mean HbA1c in the type 2 diabetes cohort was 71 mmol/mol (8.6%), and mean BMI was 30.6 kg/m2. Despite this, 19/61 (40%) were on monotherapy at time of referral, only 15/61 (25%) were on a GLP1 analog, and only 17/61 (28%) were on an SGLT2 inhibitor. Of the type 2 patients with documented BMI > 30 kg/m2, only 2/5 (40%) were on a GLP1 analog and only 2/5 (40%) were on an SGLT2 inhibitor. Lipid values were included in the referrals of 26/74 patients (35%), and blood pressure values in 25/74 (34%). Despite this, 44/74 (59%) were on a statin and 40/74 (54%) were on an ACE inhibitor or ARB. The renal function (serum creatinine or eGFR) was provided in 22/74 (30%), and information regarding microalbuminuria was provided in only 12/74 (16%). Foot examination was documented in 13/74 referrals (18%), and retinal screening status was documented in 17/74 (23%). Given the exponential increase in the numbers of patients with obesity and diabetes and increasing evidence on the importance of early multifactorial risk reduction, it is essential that cardiovascular risk factors and diabetes complications are documented and appropriate initial management commenced while patients await secondary care evaluation. Our study shows that referrals lack critical information which makes appropriate prioritization difficult. Also, the major classes of oral hypoglycaemic agents are under utilized in primary care, which exposes patients to damaging hyperglycaemia for an unnecessarily long time prior to secondary care evaluation. 1. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022;65(12):1925-66. Presentation: Thursday, June 15, 2023

Summary: Management of Hyperglycemia in Type 2 Diabetes according to the 2022 ADA-EASD Consensus Report and 2023 ADA Standards of Care in Diabetes

In October 2022, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) updated the previous consensus report for management of hyperglycemia in type 2 diabetes (T2DM). In January 2023, ADA Standards of Care in Diabetes with pharmacologic approaches to achieve a glycemic target were published to align with the consensus report by ADA and EASD. This recent consensus report and ADA Standards of Care in Diabetes emphasized weight management as an important aspect of the holistic approach to management of T2DM. In addition, it included numerous results of cardiorenal trials involving glucagon-like peptide 1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT2) inhibitor in type 2 diabetes. This information was added to address broader recommendations for cardiorenal risk reduction, in particular for organ (heart and kidney)-specific protection. This review summarizes the 2022 ADA-EASD consensus report and 2023 ADA standards of care for diabetes regarding management of hyperglycemia in T2DM.

The growing clinical effect of SGLT2 inhibitors

In September, 2015, the results of EMPA-REG OUTCOME, the first cardiovascular outcomes study based on a sodium-glucose co-transporter-2 (SGLT2) inhibitor, empagliflozin, were announced at the Annual Meeting of the European Association for the Study of Diabetes. It was the first of a series of cardiovascular outcome studies confirming a significant risk reduction of the three-point MACE (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke) in people with type 2 diabetes and established atherosclerotic cardiovascular disease. It was also the first clinical trial to show potential renal protection: empagliflozin was associated with reduced loss of estimate glomerular filtration rate compared with placebo. Moreover, the trial reported a significant reduction in the risk of hospitalisation for heart failure. 1 Zinman B Wanner C Lachin JM et al. Investigators E-ROEmpagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373: 2117-2128 Crossref PubMed Scopus (7211) Google Scholar The cardiorenal protective effects of SGLT2 inhibitors have been confirmed in subsequent cardiovascular outcomes studies done in people with type 2 diabetes 2 McGuire DK Shih WJ Cosentino F et al. Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis. JAMA Cardiol. 2021; 6: 148-158 Crossref PubMed Scopus (339) Google Scholar and without diabetes. 3 Vaduganathan M Docherty KF Claggett BL et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet. 2022; 400: 757-767 Summary Full Text Full Text PDF PubMed Scopus (61) Google Scholar Because of these results, current guidelines recommend the use of a SGLT2 inhibitor with proven beneficial effect for people with type 2 diabetes with chronic kidney disease and a history of heart failure. 4 Davies MJ Aroda VR Collins BS et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022; 65: 1925-1966 Crossref PubMed Scopus (32) Google Scholar Effects of dapagliflozin on hospitalisations in people with type 2 diabetes: post-hoc analyses of the DECLARE-TIMI 58 trialDapagliflozin reduced the risk of first and total non-elective hospitalisations for any cause in people with type 2 diabetes, regardless of the presence of atherosclerotic cardiovascular disease, including hospitalisations not directly attributed to cardiac, kidney, or metabolic causes. These findings might have implications on health-related quality of life for people with type 2 diabetes and on health-care costs attributable this condition. Full-Text PDF

SGLT2 Inhibitors: Effect on Myocardial Infarction and Stroke in Type 2 Diabetes.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently been recommended as preferred agents for management of hyperglycemia in type 2 diabetes, primarily based on their ability to reduce a composite of major cardiovascular adverse events (3-point major adverse cardiovascular events [MACE]), predominantly by reducing cardiovascular death. However, reduction of the individual components, myocardial infarction (MI), or stroke (fatal and nonfatal) events have not been well explored. In this meta-analysis, we included data available from cardiovascular outcome trials only, which were event-driven, randomized, and placebo-controlled. Pooled efficacy outcomes included Mantel Haenszel (MH) risk ratio using fixed model (with 95% CI) for fatal and nonfatal MI, stroke, and total MI and stroke. Data from 4 eligible trials included 42,568 subjects. Total MACE, MI, and stroke were reported in 4176, 2157, and 1288 subjects, respectively. SGLT2is did not significantly reduce either MI or stroke individually or in totality. The MH risk ratio (95% CI) for fatal and nonfatal MI and stroke with different SGLT2is was found to be 0.93 (95% CI, 0.85-1.01) and 1.00 (95% CI, 0.89-1.11), respectively. For total atherosclerotic cardiovascular disease (ASCVD) events, MH risk ratio (95% CI) was 0.95 (95% CI, 0.89-1.02). For all nonfatal ASCVD (combined nonfatal MI and nonfatal stroke), MH risk ratio (95% CI) was 0.94 (95% CI, 0.88-1.02). SGLT2is reduce MACE without any discernable significant reduction of the incidence of MI or stroke (fatal and nonfatal), probably implicating mechanisms unrelated to anti-atherogenic effects.

Making sense of weekly insulins

The current issue of The Lancet Diabetes & Endocrinology sees publication of a phase 2 study of the weekly insulin under development from Eli Lilly. 1 Frias J Chien J Zhang Q et al. Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study. Lancet Diabetes Endocrinol. 2023; (published online Feb 6.)https://doi.org/10.1016/S2213-8587(22)00388-6 Google Scholar Phase 2 studies have also been published from Novo Nordisk, who have further announced top-line results of a series of phase 3 studies to investors. 2 Rosenstock J Bajaj HS Janež A et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020; 383: 2107-2116 Crossref PubMed Scopus (77) Google Scholar Once-daily basal insulin is the standard starter regimen in people with type 2 diabetes, 3 Davies MJ Aroda VR Collins BS et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022; 65: 1925-1966 Crossref PubMed Scopus (20) Google Scholar and experience with other once-weekly injectables in people with type 2 diabetes, notably of GLP-1 receptor agonists, 4 Holleman C Hopcroft A Close K 3Q22 GLP-1 industry roundup. www.closeconcerns.com/knowledgebase/r/db4d2bb8Date: Nov 15, 2022 Date accessed: December 2, 2022 Google Scholar is of market preference over once-daily preparations; it is probable that clinical practice will adopt licensed weekly insulins very quickly. Weekly basal insulin might be of less relevance to people with type 1 diabetes, for whom multiple meal-time insulin doses will still be needed. Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 studyWeekly BIF achieved a similar efficacy compared with degludec despite higher fasting glucose targets in the BIF groups. Higher fasting glucose targets and lower glucose variability might have contributed to lower hypoglycaemia rates for BIF compared with degludec. These findings support continued development of BIF as a once-weekly insulin treatment for people with diabetes. Full-Text PDF

Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycemia in type 2 diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional health care team providing diabetes care in the U.S. and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the health care system, and physical activity behaviors, including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided.

Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycaemia in type 2 diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional healthcare team providing diabetes care in the USA and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the healthcare system and physical activity behaviours including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium–glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided.Graphical abstract Supplementary InformationThe online version of this article (10.1007/s00125-022-05787-2) contains peer-reviewed but unedited supplementary material.

Prevalence of Atherosclerotic Cardiovascular Disease, Heart Failure, and Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus: A Primary Care Research Network-based Study.

This study aims to assess the prevalence of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), and their combined presence in type 2 diabetes (T2D) patients in primary care for whom the 2019 ADA/EASD consensus update "Management of Hyperglycemia in Type 2 Diabetes" recommends GLP-1 receptor agonists (GLP-1RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-I) as first-line medications after metformin. Data were obtained in 2015 from Intego, a morbidity registration network of 111 general practitioners (GPs) working in 48 practices and including 123 261 registered patients. Of 123 261 patients, 9616 had T2D. Of these patients, 4200 (43.7%) presented with ASCVD and/or CKD and/or HF. Specifically, 3348 (34.8%) patients had ASCVD, 388 (4.0%) had heart failure, and 1402 (14.6%) had CKD. Compared to patients without any of these comorbidities, patients with at least 1 of these conditions were older (69.7 ±12.6 vs. 63.1±12.5 years), had higher LDL-C values (104.2±35.8 mg/dl vs. 97.2±37.7) and less frequently achieved the systolic blood pressure target of 140 mm Hg (53 vs. 61%) (all p<0.001). Comorbid patients also had significantly more other comorbidities, such as dementia or cancer; received more recommended medications, such as statins; and received less metformin. Most patients with HF (325; 3.4%) had ASCVD (114; 1.2%), CKD (76; 0.8%), or both (135; 1.4%). In total, 478 patients with CKD (5.0%) also had ASCVD. At the primary care level, 44% of T2D patients suffer from ASCVD, CKD, and/or HF, and thus qualify for GLP-1RA or SGLT2-I therapy.

The Possible Protective Effect of Metformin in COVID-19 Infection

Coronavirus 2019 (COVID-19) infections with more than 30 million confirmed cases are increasing rapidly, requiring urgent and safe treatment. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a virus responsible for the infection of COVID-19. Metformin (M) is a biguanide drug used as a first choice for the management of hyperglycemia in type 2 diabetes mellitus (T2DM). Furthermore, it is safe and currently available. It is speculated that metformin can be used for T2DM patients with COVID-19, because in addition to its hypoglycemic effect, this biguanide also shows many beneficial effects, including anti-inflammatory effects and cardiopulmonary protection especially by angiotensin converting enzyme 2 (ACE2) targeting. Therefore, the reasons for the use of metformin in COVID-19 patients were discussed in this study. Metformin has a promising role in treatment of COVID-19 in T2DM and obese women patients.

Characterization of Novel Dipeptidyl Peptidase-IV Inhibitory Peptides from Soft-Shelled Turtle Yolk Hydrolysate Using Orthogonal Bioassay-Guided Fractionations Coupled with In Vitro and In Silico Study.

Five novel peptides (LPLF, WLQL, LPSW, VPGLAL, and LVGLPL) bearing dipeptidyl peptidase IV (DPP-IV) inhibitory activities were identified from the gastrointestinal enzymatic hydrolysate of soft-shelled turtle yolk (SSTY) proteins. Peptides were isolated separately using reversed-phase (RP) chromatography in parallel with off-line strong cation exchange (SCX) chromatography followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to determine sequences. Among these peptides, LPSW showed the highest DPP-IV inhibitory activity with an IC50 value of 269.7 ± 15.91 µM. The results of the pre-incubation experiment and the kinetic study of these peptides indicated that WLQL is a true inhibitor and its inhibition toward DPP-IV is of an uncompetitive model, while LPLF, LPSW, and VPGLAL are real-substrates and competitive inhibitors against DPP-IV. The DPP-IV inhibitory peptides derived from SSTY hydrolysate in study are promising in the management of hyperglycemia in Type 2 diabetes.

Diabetes Self-management Education and Support in Adults With Type 2 Diabetes: A Consensus Report of the American Diabetes Association, the Association of Diabetes Care and Education Specialists, the Academy of Nutrition and Dietetics, the American Academy of Family Physicians, the American Academy of PAs, the American Association of Nurse Practitioners, and the American Pharmacists Association

This article is being published simultaneously in Diabetes Care, The Diabetes Educator, the Journal of the Academy of Nutrition and Dietetics, the Journal of the American Academy of Physician Assistants, the Journal of the American Association of Nurse Practitioners, and the Journal of the American Pharmacists Association. See page 13 for additional resources. Supplementary materials: Supplementary Tables 1 and 2 are available at www.jandonline.orgDiabetes is a complex and challenging disease that requires daily self-management decisions made by the person with diabetes. Diabetes self-management education and support (DSMES) addresses the comprehensive blend of clinical, educational, psychosocial, and behavioral aspects of care needed for daily self-management and provides the foundation to help all people with diabetes navigate their daily self-care with confidence and improved outcomes. 1 American Diabetes Association5. Facilitating behavior change and well-being to improve health outcomes: Standards of Medical Care in Diabetes–2020. Diabetes Care. 2020; 43: S48-S65 Crossref PubMed Scopus (200) Google Scholar ,2 Davies M.J. D’Alessio D.A. Fradkin J. et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018; 41: 2669-2701 Crossref PubMed Scopus (1401) Google Scholar This article is being published simultaneously in Diabetes Care, The Diabetes Educator, the Journal of the Academy of Nutrition and Dietetics, the Journal of the American Academy of Physician Assistants, the Journal of the American Association of Nurse Practitioners, and the Journal of the American Pharmacists Association. See page 13 for additional resources. M. A. Powers is with HealthPartners, Bloomington, MN. J. K. Bardsley is with the Medstar Health Research Institute, MedStar Diabetes Institute, and MedStar Health System Nursing, Hyattsville, MD. M. Cypress is an independent Independent consultant, Albuquerque, NM. M. M. Funnell is with the University of Michigan Medical School, Ann Arbor, MI. D. Harms is with MercyOne Clive Internal Medicine, Clive, IA. A. Hess-Fischl is with the Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, IL. B. Hooks is with Martin Army Community Hospital, Fort Benning, GA. D. Isaacs is with the Cleveland Clinic Diabetes Center, Cleveland, OH. E. D. Mandell is with Johnson & Wales University, Providence, RI. M. D. Maryniuk is with Maryniuk & Associates, Boston, MA. A. Norton is with DiabetesSisters, Chicago, IL. J. Rinker is with the Association of Diabetes Care & Education Specialists, Chicago, IL. S. Uelmen is with the Association of Diabetes Care & Education Specialists, Chicago, IL. L. M. Siminerio is with the University of Pittsburgh, Pittsburgh, PA.

Erratum. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020;43:487-493.

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PDB45 THE BUDGET IMPACT OF SITAGLIPTIN VERSUS ORAL SEMAGLUTIDE FROM A US PAYER PERSPECTIVE

Dipeptidyl peptidase 4 inhibitors are established incretin-based oral therapy for management of hyperglycemia in type 2 diabetes with sitagliptin being the most commonly prescribed drug in this class. Recently, another oral incretin-based therapy (oral glucagon-like peptide 1 receptor agonist semaglutide) was also approved for use in the same population. We estimated the budget impact of utilizing oral semaglutide vs. sitagliptin as second line agent from a US payer perspective. Using the validated IQVIA CORE Diabetes Model, the impact of treatment was simulated over a 5-year time horizon. The model captured clinical and drug costs and clinical trial data informed cohort characteristics and treatment effects. Published data on healthcare utilization costs, population estimates and current diabetes therapy treatment patterns was used. Net costs for oral semaglutide and sitagliptin were based on the recent Institute for Clinical and Economic Review (ICER) report assessing oral semaglutide. The budget impact analysis estimated additional costs associated with oral semaglutide instead of sitagliptin for a US payer covering 1 million lives and for the total US population. In a hypothetical plan of 1 million patient lives, 13,134 patients would currently be on second-line treatment with 1,988 using sitagliptin. Over a 5-year time horizon, each 10% increase in the use of oral semaglutide instead of sitagliptin would result in an additional cost of $3.4M for a US payer. Extrapolating to the additional cost for the entire US population, the value would be $1.2B. Switching 50% of sitagliptin patients to oral semaglutide would yield costs of $17.1 M for the hypothetical plan and $5.6B for the US population. Use of oral semaglutide instead of sitagliptin results in substantial incremental costs to a US payer over a 5-year time horizon.

2019 update to: Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

2019 update to: Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycaemia, based on important research findings from large cardiovascular outcomes trials published in 2019. Important changes include: (1) the decision to treat high-risk individuals with a glucagon-like-peptide 1 (GLP-1) receptor agonist or sodium-glucose cotransporter 2 (SGLT2) inhibitor to reduce major adverse cardiovascular events (MACE), hospitalisation for heart failure (hHF), cardiovascular death or chronic kidney disease (CKD) progression should be considered independently of baseline HbA1c or individualised HbA1c target; (2) GLP-1 receptor agonists can also be considered in patients with type 2 diabetes without established cardiovascular disease (CVD) but with the presence of specific indicators of high risk; and (3) SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure, particularly those with heart failure with reduced ejection fraction, to reduce hHF, MACE and CVD death, as well as in patients with type 2 diabetes with CKD (eGFR 30 to ≤60mlmin-1 [1.73m]-2 or urinary albumin-to-creatinine ratio >30mg/g, particularly >300mg/g) to prevent the progression of CKD, hHF, MACE and cardiovascular death.

2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycemia, based on important research findings from large cardiovascular outcomes trials published in 2019. Important changes include: 1) the decision to treat high-risk individuals with a glucagon-like peptide 1 (GLP-1) receptor agonist or sodium–glucose cotransporter 2 (SGLT2) inhibitor to reduce major adverse cardiovascular events (MACE), hospitalization for heart failure (hHF), cardiovascular death, or chronic kidney disease (CKD) progression should be considered independently of baseline HbA1c or individualized HbA1c target; 2) GLP-1 receptor agonists can also be considered in patients with type 2 diabetes without established cardiovascular disease (CVD) but with the presence of specific indicators of high risk; and 3) SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure, particularly those with heart failure with reduced ejection fraction, to reduce hHF, MACE, and CVD death, as well as in patients with type 2 diabetes with CKD (estimated glomerular filtration rate 30 to ≤60 mL min–1 [1.73 m]–2 or urinary albumin-to-creatinine ratio >30 mg/g, particularly >300 mg/g) to prevent the progression of CKD, hHF, MACE, and cardiovascular death.

SGLT2 inhibitor or GLP-1 receptor agonist in type 2 diabetes?

Among the newest glucose-lowering agents for the treatment of type 2 diabetes, two classes raise much interest: glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Indeed, both showed a cardiovascular protection in dedicated outcome studies in patients with type 2 diabetes at high cardiovascular risk. 1 Scheen AJ Cardiovascular outcome studies in type 2 diabetes: comparison between SGLT2 inhibitors and GLP-1 receptor agonists. Diabetes Res Clin Pract. 2018; 143: 88-100 Summary Full Text Full Text PDF PubMed Scopus (35) Google Scholar , 2 Zelniker TA Wiviott SD Raz I et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019; 139: 2022-2031 Crossref PubMed Scopus (273) Google Scholar These findings had a major effect on the newer guidelines for the management of type 2 diabetes. In patients with atherosclerotic cardiovascular disease, guidelines now recommend, after failure of metformin monotherapy, the addition of a GLP-1 receptor agonist or an SGLT2 inhibitor that was shown to reduce the risk of major cardiovascular events. 3 Davies MJ D'Alessio DA Fradkin J et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018; 61: 2461-2498 Crossref PubMed Scopus (604) Google Scholar In the absence of heart failure or renal disease, two conditions in which SGLT2 inhibitors appear more protective, 2 Zelniker TA Wiviott SD Raz I et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019; 139: 2022-2031 Crossref PubMed Scopus (273) Google Scholar the clinician can choose between these two pharmacological options without specific guidance in the absence of comparative trials. 3 Davies MJ D'Alessio DA Fradkin J et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018; 61: 2461-2498 Crossref PubMed Scopus (604) Google Scholar Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trialOnce-weekly semaglutide 1·0 mg was superior to daily canagliflozin 300 mg in reducing HbA1c and bodyweight in patients with type 2 diabetes uncontrolled on metformin therapy. These outcomes might guide treatment intensification choices. Full-Text PDF

Abstract 112: Soluble (pro) Renin Receptor Serves as Novel Insulin Sensitizing Agent in Mice With Diet-Induced Obesity

Thiazolidinediones, the PPARgamma agonists, represent a unique class of insulin sensitizers for management of hyperglycemia in type 2 diabetes but are limited by the side effect of fluid retention. Here we report therapeutic potential of histidine-tagged recombinant soluble (pro)renin receptor (sPRR), termed as sPRR-His, in a mouse obesity model induced by 9-month high fat diet (DIO) for management of glucose dysregulation. In the DIO mice, a 2-wk administration of sPRR-His lowered body weight (47.0 ± 1.4 vs. 52.8 ± 1.2 g) and remarkably improved multiple metabolic parameters including hyperglycemia (serum glucose: 148.8 ± 19.1 vs. 224.8 ± 12.5 mg/dL), hyperinsulinemia (serum insulin: 3.7 ± 0.4 vs. 10.9 ± 0.9 ng/ml), glucose intolerance, albuminuria (urine albumin/ Creatinine: 63.4 ± 3.5 vs. 97.7 ± 10.2 mg/g), and glomerular hyperfiltration (GFR: 264.7 ± 12.2 vs. 521.3 ± 18.2 μl/min) in the absence of fluid retention (plasma volume: 28.7 ± 1.2 vs. 27.8 ± 0.9 μl/g). GFR and plasma volume were measured by using FITC-sinistrin (7.5mg/100g i.v.) and FITC-dextran (2 mg/100 g i.v.) respectively. Conversely, inhibition of endogenous sPRR production by PF429242, an inhibitor of site-1 protease induced diabetes and insulin resistance which were reversed by sPRR-His supplement. At cellular level, sPRR-His enhanced insulin-induced increases in glucose uptake via upregulation of phosphorylated AKT and protein abundance of Glut4. Promoter and gene expression analysis revealed PRR as a direct target gene of PPARγ. Adipocyte-specific PPARγ deletion induced severe diabetes (blood glucose: 243.6 ± 39.8 vs. 108.4 ± 2.1 mg/dL) and insulin resistance (plasma insulin: 48.9 ± 4 vs. 1.5 ± 0.2 ng/ml) associated with reduced adipose PRR expression and circulating sPRR (plasma sPRR: 265.7 ± 14 vs. 893.0 ± 86.8 pg/ml). sPRR-His supplement in the null mice nearly normalized blood glucose (142.4 ± 12.2 mg/dL) and insulin level (14.3 ± 7.9 ng/ml). Additionally, sPRR-His treatment suppressed DIO-induced renal sodium-glucose cotransporter-2 (SGLT2) expression. Overall, sPRR-His exerts potent hypoglycemic action via serving as a mediator of insulin-sensitizing action of thiazolidinedione as well as a negative regulator of renal SGLT2 in the absence of fluid retention side effect.

Management of hyperglycaemia in type 2 diabetes. Consensus Report 2018 by the ADA and EASD

Ende letzten Jahres wurde ein aktualisierter ADA/EASD-Konsensbericht veroffentlicht. Die Experten — funf aus Europa und funf aus den USA — berucksichtigten dafur aktuelle klinische Studien zur Therapie des Typ-2-Diabetes. Der Autor des nachfolgenden Beitrags fasst die Umsetzung in der Praxis zusammen.