Disparities in prevalence and treatment of diabetes, cardiovascular and chronic kidney diseases - Recommendations from the taskforce of the guideline workshop.

There is a mounting clinical, psychosocial, and socioeconomic burden worldwide as the prevalence of diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD) continues to rise. Despite the introduction of therapeutic interventions with demonstrated efficacy to prevent the development or progression of these common chronic diseases, many individuals have limited access to these innovations due to their race/ethnicity, and/or socioeconomic status (SES). However, practical guidance to providers and healthcare systems for addressing these disparities is often lacking. In this article, we review the prevalence and impact of healthcare disparities derived from the above-mentioned chronic conditions and present broad-based recommendations for improving access to quality care and health outcomes within the most vulnerable populations.

[Kidney diseases in type 2 diabetes mellitus : Overview and implementation of guidelines, position papers and practical recommendations for diagnostics and monitoring]. / Nierenerkrankungen bei Diabetes mellitus Typ 2 : Überblick und Implementierung der Leitlinien, Positionspapiere und Praxisempfehlungen zur Diagnostik und Überwachung.

BACKGROUND: National and international medical societies have published guidelines and recommendations pertaining to the diagnostics and monitoring of chronic kidney disease in patients with type 2 diabetes mellitus. Consistency and implementation in daily clinical practice are rarely reported. OBJECTIVE: This article provides an overview on recommendations as a reflection of the global state of the art and assesses the implementation in daily practice in Germany, which was collected via a representative questionnaire. MATERIAL AND METHODS: The current guidelines were compared with respect to the consistency of parameters, frequency of testing and recommendations for nephrological referrals. The results were then compared with the survey responses to estimate the level of their implementation in daily practice in Germany. RESULTS: According to the recommendations the estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (UACR) should be tested at least once per year in all patients with type 2 diabetes. In cases of more severe kidney impairment (above Kidney Disease:Improving Global Outcomes, KDIGO, stage 3b with eGFR < 45 ml/min/1,73 m2) or albuminuria (from stage A2), more frequent measurements and nephrological referrals are recommended; however, different threshold values and frequencies are recommended. The responses from the questionnaires indicate that eGFR is tested annually in 96.5% of all cases and albuminuria is tested in 77.2% of cases. An eGRF triggered referral to a nephrologist is implemented by 19.6% of all nonnephrological practitioners, albuminuria triggered referrals are implemented in the majority of cases. CONCLUSION: Measurement of eGFR is the established standard in Germany. Potential improvement was found in albumin measurement, the frequency of testing and the time point for nephrological consultation. All guidelines emphasize the benefits of interdisciplinary cooperation.

Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop.

In recent years, several novel agents have become available to treat individuals with type 2 diabetes (T2D), such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), tirzepatide, which is a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA)/glucagon-like peptide-1 receptor agonist (GLP-1 RA), and finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA) that confers significant renal and cardiovascular benefits in individuals with (CKD). New medications have the potential to improve the lives of individuals with diabetes. However, clinicians are challenged to understand the benefits and potential risks associated with these new and emerging treatment options. In this article, we discuss how use of network meta-analyses (NMA) can fill this need.

[Diabetes mellitus and cardiovascular prevention]. / Diabetes mellitus und kardiovaskuläre Prävention.

Diabetes mellitus is the most common metabolic disease with >500 million people affected worldwide and currently 8,7 million in Germany. About 90% of diabetes cases are due to type 2 diabetes mellitus (T2D). This form of diabetes is characterized by an increased release of proinflammatory adipokines, endothelial dysfunction and hyperglycemia, among others. Hypertension and dyslipidemia are also very commonly present. The prevalence of cardiovascular disease is about 2-3 times higher in T2D than in age-matched individuals without a diagnosis of diabetes. Cardiovascular mortality is also about twice as high in people with diabetes compared to a non-diabetic population. People with diabetes are therefore generally considered a high-risk cardiovascular group and require special attention in the diagnosis and treatment of cardiovascular disease. Contributing factors to reduce high cardiovascular risk include a healthy lifestyle, normalization of blood pressure, optimization of blood lipid levels, and specific diabetes therapy tailored to cardiovascular risk. This review addresses the specific treatment options for reducing cardiovascular risk in patients with diabetes mellitus.

Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial.

BACKGROUND: Insulin icodec (icodec) is a once-weekly basal insulin currently under development. ONWARDS 2 aimed to assess the efficacy and safety of once-weekly icodec versus once-daily insulin degludec (degludec) in basal insulin-treated type 2 diabetes. METHODS: This 26-week, randomised, open-label, active-controlled, multicentre, treat-to-target phase 3a trial was conducted in 71 sites in nine countries. Eligible participants with type 2 diabetes inadequately controlled on once-daily or twice-daily basal insulin, with or without non-insulin glucose-lowering agents, were randomly assigned (1:1) to once-weekly icodec or once-daily degludec. The primary outcome was change from baseline to week 26 in HbA1c; the margin used to establish non-inferiority of icodec compared with degludec was 0·3 percentage points. Safety outcomes (hypoglycaemic episodes and adverse events) and patient-reported outcomes were also assessed. The primary outcome was evaluated in all randomly assigned participants; safety outcomes were evaluated descriptively based on all randomly assigned participants who received at least one dose of trial product, with statistical analyses based on all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04770532, and is now complete. FINDINGS: Between March 5 and July 19, 2021, 635 participants were screened, of whom 109 were ineligible or withdrew, and 526 were randomly assigned to icodec (n=263) or degludec (n=263). From a mean baseline of 8·17% (icodec; 65·8 mmol/mol) and 8·10% (degludec; 65·0 mmol/mol), HbA1c was reduced to a greater extent with icodec than degludec (7·20% vs 7·42% [55·2 vs 57·6 mmol/mol], respectively) at week 26. This translates to an estimated treatment difference (ETD) of -0·22 percentage points (95% CI -0·37 to -0·08) or -2·4 mmol/mol (95% CI -4·1 to -0·8), demonstrating non-inferiority (p<0·0001) and superiority (p=0·0028). The estimated mean change from baseline to week 26 in bodyweight was +1·40 kg for icodec and -0·30 kg for degludec (ETD 1·70 [95% CI 0·76 to 2·63]). Overall rates of combined level 2 or level 3 hypoglycaemia were less than one event per patient-year of exposure for both groups (0·73 [icodec] vs 0·27 [degludec]; estimated rate ratio 1·93 [95% CI 0·93 to 4·02]). Overall, 161 (61%) of 262 participants receiving icodec and 134 (51%) of 263 participants receiving degludec experienced an adverse event; 22 (8%) and 16 (6%), respectively, experienced a serious adverse event. One serious adverse event (degludec) was assessed as being possibly related to treatment. No new safety issues were identified in relation to icodec compared with degludec in this trial. INTERPRETATION: Among adults with basal insulin-treated type 2 diabetes, treatment with once-weekly icodec versus once-daily degludec demonstrated non-inferiority and statistical superiority in HbA1c reduction after 26 weeks, associated with modest weight gain. Overall rates of hypoglycaemia were low, with numerically but not statistically significantly higher event rates of level 2 or level 3 hypoglycaemia with icodec versus degludec. FUNDING: Novo Nordisk.

Guideline Development for Medical Device Technology: Issues for Consideration.

Advances in the development of innovative medical devices and telehealth technologies create the potential to improve the quality and efficiency of diabetes care through collecting, aggregating, and interpreting relevant health data in ways that facilitate more informed decisions among all stakeholder groups. Although many medical societies publish guidelines for utilizing these technologies in clinical practice, we believe that the methodologies used for the selection and grading of the evidence should be revised. In this article, we discuss the strengths and limitations of the various types of research commonly used for evidence selection and grading and present recommendations for modifying the process to more effectively address the rapid pace of device and technology innovation and new product development.

Effect of once-weekly semaglutide versus thrice-daily insulin aspart, both as add-on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open-label, multinational, phase 3b trial.

AIM: To compare the efficacy and safety of once-weekly (OW) semaglutide versus thrice-daily (TID) insulin aspart (IAsp) in participants with inadequately controlled type 2 diabetes (T2D) treated with insulin glargine (IGlar) and metformin. MATERIALS AND METHODS: SUSTAIN 11 (NCT03689374) was a randomized (1:1), parallel, open-label, multinational, phase 3b trial. After a 12-week run-in to optimize once-daily IGlar U100, 1748 adults with T2D (HbA1c >7.5% to ≤10.0%) were randomized to OW semaglutide or TID IAsp as add-on to optimized IGlar and metformin for 52 weeks. The primary outcome was change in HbA1c from randomization to week 52. Confirmatory secondary endpoints included the occurrence of severe hypoglycaemic episodes and change in body weight (BW). Safety was assessed. RESULTS: HbA1c (randomization: 8.6% [70.0 mmol/mol]) decreased by 1.5% points (16.6 mmol/mol) and 1.2% points (13.4 mmol/mol) with semaglutide (n = 874) and IAsp (n = 874), respectively (estimated treatment difference [ETD] -0.29% points [95% confidence interval {CI} -0.38; -0.20]; P < .0001 for non-inferiority). Few severe hypoglycaemic episodes were recorded in either group, with no statistically significant difference between the groups. Change in BW from randomization (87.9 kg) to week 52 was in favour of semaglutide (-4.1 kg) versus IAsp (+2.8 kg) (ETD -6.99 kg [95% CI -7.41; -6.57]). A higher proportion of participants experienced adverse events with semaglutide (58.5%) versus IAsp (52.1%); most were mild to moderate. CONCLUSIONS: In this basal insulin-treated population, OW semaglutide improved glycaemic control to a greater extent than TID IAsp and provided numerically greater weight loss.

Considering Insulin Secretory Capacity as Measured by a Fasting C-Peptide/Glucose Ratio in Selecting Glucose-Lowering Medications.

Type 2 diabetes mellitus is a heterogeneous disease. Recently introduced new subclassifications promise more efficacious, tailored treatments which could complement current guidelines. In the differentiation of the new diabetes subphenotypes, assessment of insulin secretion is one of the essential components. Based on a large number of insulin secretion measurements, we propose fasting C-peptide/glucose ratio (CGR) as an adequate and practicable estimate of insulin secretion. CGR discriminates insulin deficiency from insulin hypersecretion. We suggest using insulin secretion, determined from CGR, as an essential input for therapeutic decisions at the beginning or modification of diabetes treatment. Furthermore, we propose 3 practical steps to guide decisions in the subtype-specific therapy of diabetes mellitus. The first step consists of detecting insulin deficiency indicated by a low CGR with the need for immediate insulin therapy. The second step is related to high CGR and aims at lowering cardiovascular risk associated with diabetes. The third step is the consideration of a de-escalation of glucose-lowering therapy in individuals with mild diabetes subphenotypes.

Towards living guidelines on cardiorenal outcomes in diabetes: A pilot project of the Taskforce of the Guideline Workshop 2020.

In June 2020, the Taskforce of the Guideline Workshop 2019 convened via teleconferencing to initiate a pilot project that demonstrates the various processes and considerations involved in developing high-quality, evidence-based clinical practice guidelines for the medical management of individuals with type 2 diabetes (T2D) and its associated comorbidities, including cardiovascular disease (CVD) and chronic kidney disease (CKD). The goal of the pilot project was to create evidence-based guidelines for use of sodium-glucose transport protein 2 inhibitors (SGLT2-I) when managing very high risk T2D patients, evidenced by the presence of both CVD and CKD. For this purpose the Taskforce represented a guideline panel and made use of synthesized evidence from an ongoing BMJ Rapid Recommendations project on SGLT2-I and GLP-1 receptor agonists. Results from the Taskforce pilot project demonstrated the value, feasibility and utility of using a step-wise approach to identifying and grading evidence and then developing actionable recommendations for utilizing SGLT2-I in this at-risk T2D population. This report describes the various steps involved in the process and explains how it can be utilized to rapidly develop recommendations in a format that is easy to use and can be quickly updated as new evidence becomes available, also within the emerging concept of living guidelines.

Metformin Associated Lactic Acidosis in Clinical Practice - A Case Series.

AIMS: The aim of this case report is to specify the frequency and mortality of Metformin-Associated Lactic Acidosis (MALA) in emergency medicine, as the diagnosis seems to occur more often than estimated. METHODS: To identify the subjects, we developed screening criteria for MALA. We measured the serum metformin concentration to confirm the diagnosis in all patients fulfilling these criteria. Retrospectively the patients were grouped according to individual risk (according to a defined risk score) and the application of renal replacement therapy. RESULTS: From 2013 until 2018 we were able to identify 11 MALA patients revealing a frequency of 1:4,000 emergency patients. Six patients survived and five died in the follow-up. All three patients in the high-risk group died although all of them received renal replacement therapy. In the low-risk group (three patients, one with renal replacement therapy), all patients survived, while in the intermediate-risk group (five patients, one with renal replacement therapy) three patients survived and two died. Additional severe comorbidities also contributed to mortality. CONCLUSIONS: Every patient matching the screening criteria of acute renal failure, lactic acidosis and continued intake of metformin can be considered a potential MALA case. A risk score assessment which includes severe comorbidities may help to identify high-risk individuals and should be evaluated in larger studies.To prevent MALA, patients should be trained to immediately interrupt their own metformin use when showing signs of volume depletion. Physicians should be aware of the additional risk factors such as co-medication with diuretics, ACE (angiotensin converting enzyme) ACE inhibitors and NSAIDs (non steroidal anti inflammatory drugs).

Proceedings of the Guideline Workshop 2019: Strategies for the Optimization of Guideline Processes in Diabetes, Cardiovascular Diseases, and Kidney Diseases.

The Guideline Workshop 2019, held in October 2019 in Munich, Germany, had the purpose of facilitating discussion on strategies for optimization of guideline processes in diabetes among a group of representatives of renown national and international societies in the field of diabetes, cardiology, and nephrology. Results of this panel's discussions are presented in this article and comprise a variety of suggestions for improving the quality and usability of guidelines, as well as to accelerate the development and responsiveness of guidelines to newly published, relevant data from clinical trials such as cardiovascular outcome trials in diabetes mellitus. These include, but are not limited to, recommendations to optimize presentation of content in guidelines, use of the Grading of Recommendations Assessment, Development, and Evaluation approach to rating the quality of evidence to harmonize guidelines, and utilization of digital health technologies to accelerate, streamline, and optimize communication on relevant data and development of clinical guidelines and necessary updates, while reducing costs. Recognizing that achieving alignment in guideline development among various medical organizations will be a long-term process, representatives from cross-sectional medical organizations relevant to cardio/renal metabolic disease and experts in guideline methodology will work together in the future. Among other activities, it is planned to continue the activity and organize a Guideline Workshop in 2020.

Proceedings of the Guideline Workshop 2019 - Strategies for the optimization of guideline processes in diabetes, cardiovascular diseases and kidney diseases.

The Guideline Workshop 2019, held in October 2019 in Munich, Germany, had the purpose of facilitating discussion on strategies for optimization of guideline processes in diabetes amongst a group of representatives of renown national and international societies in the field of diabetes, cardiology, and nephrology. Results of this panel's discussions are presented in this manuscript and comprise a variety of suggestions for improving the quality and usability of guidelines, as well as to accelerate the development and responsiveness of guidelines to newly published, relevant data from clinical trials such as cardiovascular outcome trials in diabetes mellitus. These include, but are not limited to, recommendations to optimize presentation of content in guidelines, use of the GRADE-approach to rating the quality of evidence to harmonize guidelines, and utilization of digital health technologies to accelerate, streamline, and optimize communication on relevant data and development of clinical guidelines and necessary updates, while reducing costs. Recognizing that achieving alignment in guideline development among various medical organizations will be a long-term process, representatives from cross-sectional medical organizations relevant to cardio-renal metabolic disease and experts in guideline methodology will work together in the future. Among other activities, it is planned to continue the activity and organize a Guideline Workshop in 2020.

Critical Reappraisal of the Time-in-Range: Alternative or Useful Addition to Glycated Hemoglobin?

The HbA1c value is a well-established parameter used to characterize glucose control. Continuous glucose monitoring (CGM)-derived parameters calculated using daily glucose profiles such as Time-in-Range (TiR) have increasingly been gaining interest for assessing a patient's current therapy. The question has arisen as to whether TiR could replace HbA1c? Because TiR focuses on the current quality of glucose control during a minimum of 10 to 14 days of CGM use and reflects the variability of glucose concentrations. Time-in-Range could be considered an attractive option for improving diabetes control in patients with diabetes. Due to the lack of established standards for glucose measurements with CGM systems, results from different CGM systems can deviate from each other. Time-in-Range should not be viewed as a replacement for HbA1c, but should be used to deliver valuable additional information.

[Pitfalls in the Diagnosis of Diabetes: Are we too Lax with Laboratory Parameters?] / Fallstricke bei der Diabetesdiagnostik: Wird zu lax mit Laborwerten umgegangen?

The diagnosis of diabetes is associated with pre-analytical and analytical problems. Fasting glucose (FG), oral glucose tolerance test (oGTT) and HbA1c have advantages and shortcomings and have no equal diagnostic validity. oGTT is the most sensitive test, but its reproducibility is rather poor (CV±â€Š15 %). FG detects only 70 - 80 % of overt diabetes. FG is falsified by inappropriate blood sampling, intra-individual fluctuations and mistakes with the oGTT. HbA1c despite IFC- standardization, but with a tolerable coefficient of variation of ±â€Š18 % in round robin tests and use of not commutable control material is not easy to interpret. HbA1c analysis shows also interferences and is therefore of limited diagnostic value. Its threshold value of ≥ 6.5 % (≥ 48 mmol/mol Hb) is based on consensus and not on evidence. The diagnostic effort (FG and/or oGTT+HbA1c) with serious consequences is minimal invasive, reasonable and cheap. It prevents over- and underdiagnosis.

Efficacy and safety of dapagliflozin or dapagliflozin plus saxagliptin versus glimepiride as add-on to metformin in patients with type 2 diabetes.

OBJECTIVE: To compare the efficacy and safety of dapagliflozin and dapagliflozin plus saxagliptin vs glimepiride as add-on to metformin in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This 52-week, multicentre, double-blind, active-controlled study (NCT02471404) randomized (1:1:1) patients (n = 939; HbA1c 7.5%-10.5%) on metformin monotherapy (≥1500 mg/day) to add-on dapagliflozin 10 mg, dapagliflozin 10 mg plus saxagliptin 5 mg, or glimepiride 1 to 6 mg (titrated). The primary efficacy end point was change in HbA1c from baseline to Week 52. RESULTS: Baseline mean age, diabetes duration and HbA1c were 58.4 years, 7.0 years and 8.3%, respectively. Adjusted mean HbA1c change from baseline was -1.20% with dapagliflozin plus saxagliptin and -0.82% with dapagliflozin, vs -0.99% with glimepiride (mean dose at Week 52, 4.6 mg). Changes in body weight (-3.2 kg and -3.5 kg vs +1.8 kg) and systolic blood pressure (SBP; -6.4 mm Hg and -5.6 mm Hg vs -1.6 mm Hg) were significantly greater with dapagliflozin plus saxagliptin and dapagliflozin than with glimepiride. FPG decreased significantly with dapagliflozin plus saxagliptin compared with glimepiride (-2.1 mmol/L vs -1.5 mmol/L) and was similar with dapagliflozin (-1.6 mmol/L) compared with glimepiride. Confirmed incidence of hypoglycaemia was lower with dapagliflozin regimens than with glimepiride (0 and 1 vs 13 patients) and fewer patients required rescue. Genital infections were more frequent with dapagliflozin; other AE profiles were similar. CONCLUSIONS: Dapagliflozin, saxagliptin and metformin improved glycaemic control compared with glimepiride plus metformin; add-on of dapagliflozin alone showed efficacy similar to that of glimepiride. Both dapagliflozin regimens decreased body weight and SBP, with a lower incidence of hypoglycaemia compared with glimepiride.