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.
Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes
The LEAD (Liraglutide Effect and Action in Diabetes)-2 study
Michael ...Nauck , MD, PHD 1 ,
Anders Frid , MD 2 ,
Kjeld Hermansen , MD 3 ,
Nalini S. Shah , MD 4 ,
Tsvetalina Tankova , MD 5 ,
Ismail H. Mitha , MD 6 ,
Milan Zdravkovic , MD, PHD 7 ,
Maria Düring , PHD 7 ,
David R. Matthews , MD 8 and
for the LEAD-2 Study Group
1 Diabeteszentrum Bad Lauterberg, Harz, Germany
2 Öresund Diabetes Team AB, Lund, Sweden
3 Aarhus University Hospital, Aarhus, Denmark
4 Seth G.S. Medical College and KEM Hospital, Mumbai, India
5 Clinic of Diabetology, Sophia, Bulgaria
6 Benmed Hospital, Benoni, Republic of South Africa
7 Novo Nordisk, Bagsvaerd, Denmark
8 Oxford Centre for Diabetes Endocrinology and Metabolism, Oxford, U.K.
Corresponding author: Michael A. Nauck, nauck{at}diabeteszentrum.de
Abstract
OBJECTIVE —The efficacy and safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to metformin were compared with
addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes (OAD) therapy.
RESEARCH DESIGN AND METHODS —In this 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial, 1,091 subjects were randomly
assigned (2:2:2:1:2) to once-daily liraglutide (either 0.6, 1.2, or 1.8 mg/day injected subcutaneously), to placebo, or to
glimepiride (4 mg once daily). All treatments were in combination therapy with metformin (1g twice daily). Enrolled subjects
(aged 25–79 years) had type 2 diabetes, A1C of 7–11% (previous OAD monotherapy for ≥3 months) or 7–10% (previous OAD combination
therapy for ≥3 months), and BMI ≤40 kg/m 2 .
RESULTS —A1C values were significantly reduced in all liraglutide groups versus the placebo group ( P < 0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide, and glimepiride and 0.7% for 0.6 mg liraglutide
and an increase of 0.1% for placebo. Body weight decreased in all liraglutide groups (1.8–2.8 kg) compared with an increase
in the glimepiride group (1.0 kg; P < 0.0001). The incidence of minor hypoglycemia with liraglutide (∼3%) was comparable to that with placebo but less than that
with glimepiride (17%; P < 0.001). Nausea was reported by 11–19% of the liraglutide-treated subjects versus 3–4% in the placebo and glimepiride groups.
The incidence of nausea declined over time.
CONCLUSIONS —In subjects with type 2 diabetes, once-daily liraglutide induced similar glycemic control, reduced body weight, and lowered
the occurrence of hypoglycemia compared with glimepiride, when both had background therapy of metformin.
Footnotes
Published ahead of print at http://care.diabetesjournals.org on 17 October 2008. Clinical trial reg. no. NCT00318461, clinicaltrials.gov.
*A complete list of the LEAD-2 study investigators can be found in an online appendix available at http://dx.doi.org/10.2337/dc08-1355 .
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted September 28, 2008.
Received July 22, 2008.
DIABETES CARE
The disclosure of proven cardiorenal benefits with certain antidiabetic agents was supposed to herald a new era in the management of type 2 diabetes (T2D), especially for the many patients with T2D ...who are at high risk for cardiovascular and renal events. However, as the evidence in favour of various sodium-glucose transporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) accumulates, prescriptions of these agents continue to stagnate, even among eligible, at-risk patients. By contrast, dipeptidyl peptidase-4 inhibitors (DPP-4i) DPP-4i remain more widely used than SGLT2i and GLP-1 RA in these patients, despite a similar cost to SGLT2i and a large body of evidence showing no clear benefit on cardiorenal outcomes. We are a group of diabetologists united by a shared concern that clinical inertia is preventing these patients from receiving life-saving treatments, as well as placing them at greater risk of hospitalisation for heart failure and progression of renal disease. We propose a manifesto for change, in order to increase uptake of SGLT2i and GLP-1 RA in appropriate patients as a matter of urgency, especially those who could be readily switched from an agent without proven cardiorenal benefit. Central to our manifesto is a shift from linear treatment algorithms based on HbA1c target setting to parallel, independent considerations of atherosclerotic cardiovascular disease, heart failure and renal risks, in accordance with newly updated guidelines. Finally, we call upon all colleagues to play their part in implementing our manifesto at a local level, ensuring that patients do not pay a heavy price for continued clinical inertia in T2D.
To evaluate chronic kidney disease (CKD) and cardiovascular outcomes in TECOS (Clinical trial reg. no. NCT00790205, clinicaltrials.gov) participants with type 2 diabetes and cardiovascular disease ...treated with sitagliptin, a dipeptidyl peptidase 4 inhibitor, according to baseline estimated glomerular filtration rate (eGFR).
We used data from 14,671 TECOS participants assigned in a double-blind design to receive sitagliptin or placebo added to existing therapy, while aiming for glycemic equipoise between groups. Cardiovascular and CKD outcomes were evaluated over a median period of 3 years, with participants categorized at baseline into eGFR stages 1, 2, 3a, and 3b (≥90, 60-89, 45-59, or 30-44 mL/min/1.73 m
, respectively).
Participants with eGFR stage 3b were older, were more often female, and had a longer duration of diabetes. Four-point major adverse cardiovascular event rates increased with lower baseline eGFR (3.52, 3.55, 5.74, and 7.34 events/100 patient-years for stages 1-3b, respectively). Corresponding adjusted hazard ratios for stages 2, 3a, and 3b versus stage 1 were 0.93 (95% CI 0.82-1.06), 1.28 (1.10-1.49), and 1.39 (1.13-1.72), respectively. Sitagliptin therapy was not associated with cardiovascular outcomes for any eGFR stage (interaction P values were all >0.44). Kidney function declined at the same rate in both treatment groups, with a marginally lower but constant eGFR difference (-1.3 mL/min/1.73 m
) in those participants who were assigned to sitagliptin. Treatment differences in these eGFR values remained after adjustment for region, baseline eGFR, baseline HbA
, time of assessment, and within-study HbA
levels.
Impaired kidney function is associated with worse cardiovascular outcomes. Sitagliptin has no clinically significant impact on cardiovascular or CKD outcomes, irrespective of baseline eGFR.
To describe the design of the Feel4Diabetes-intervention and the baseline characteristics of the study sample.
School- and community-based intervention with cluster-randomized design, aiming to ...promote healthy lifestyle and tackle obesity and obesity-related metabolic risk factors for the prevention of type 2 diabetes among families from vulnerable population groups. The intervention was implemented in 2016-2018 and included: (i) the 'all-families' component, provided to all children and their families via a school- and community-based intervention; and (ii) an additional component, the 'high-risk families' component, provided to high-risk families for diabetes as identified with a discrete manner by the FINDRISC questionnaire, which comprised seven counselling sessions (2016-2017) and a text-messaging intervention (2017-2018) delivered by trained health professionals in out-of-school settings. Although the intervention was adjusted to local needs and contextual circumstances, standardized protocols and procedures were used across all countries for the process, impact, outcome and cost-effectiveness evaluation of the intervention.
Primary schools and municipalities in six European countries.
Families (primary-school children, their parents and grandparents) were recruited from the overall population in low/middle-income countries (Bulgaria, Hungary), from low socio-economic areas in high-income countries (Belgium, Finland) and from countries under austerity measures (Greece, Spain).
The Feel4Diabetes-intervention reached 30 309 families from 236 primary schools. In total, 20 442 families were screened and 12 193 'all families' and 2230 'high-risk families' were measured at baseline.
The Feel4Diabetes-intervention is expected to provide evidence-based results and key learnings that could guide the design and scaling-up of affordable and potentially cost-effective population-based interventions for the prevention of type 2 diabetes.
Type 2 diabetes mellitus (T2DM) comprises the vast majority of all diabetes cases in adults, with alarmingly increasing prevalence over the past few decades worldwide. A particularly heavy healthcare ...burden of diabetes is noted in Europe, where 8.8% of the population aged 20-79 years is estimated to have diabetes according to the International Diabetes Federation. Multiple risk factors are implicated in the pathogenesis of T2DM with complex underlying interplay and intricate gene-environment interactions. Thus, intense research has been focused on studying the role of T2DM risk factors and on identifying vulnerable groups for T2DM in the general population which can then be targeted for prevention interventions.
For this narrative review, we conducted a comprehensive search of the existing literature on T2DM risk factors, focusing on studies in adult cohorts from European countries which were published in English after January 2000.
Multiple lifestyle-related and sociodemographic factors were identified as related to high T2DM risk, including age, ethnicity, family history, low socioeconomic status, obesity, metabolic syndrome and each of its components, as well as certain unhealthy lifestyle behaviors. As Europe has an increasingly aging population, multiple migrant and ethnic minority groups and significant socioeconomic diversity both within and across different countries, this review focuses not only on modifiable T2DM risk factors, but also on the impact of pertinent demographic and socioeconomic factors.
In addition to other T2DM risk factors, low socioeconomic status can significantly increase the risk for prediabetes and T2DM, but is often overlooked. In multinational and multicultural regions such as Europe, a holistic approach, which will take into account both traditional and socioeconomic/socioecological factors, is becoming increasingly crucial in order to implement multidimensional public health programs and integrated community-based interventions for effective T2DM prevention.
Abstract Aim To evaluate the performance of FINDRISC as a screening tool for prediabetes – impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and undetected diabetes (UDD) in ...subjects at risk of developing diabetes. Subjects and methods 2169 subjects with at least one risk factor for diabetes completed the FINDRISC questionnaire and underwent an oral glucose tolerance test. FINDRISC performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC). Results 56.6% of subjects demonstrated normal glucose tolerance (NGT), 14.5% – IFG, 11.4% – IGT and 17.5% – UDD. NGT group demonstrated mean FINDRISC 10.1 ± 3.4, IFG group – 13.8 ± 4.3 ( p < 0.0001 vs. NGT), IGT group – 14.4 ± 5.4 ( p < 0.0001 vs. NGT) and UDD group – 15.5 ± 4.8 ( p < 0.0001 vs. NGT and IFG, p < 0.01 vs. IGT). The AUC-ROC was 0.70 (95% CI 0.67–0.73) for UDD and 0.71 (95% CI 0.69–0.73) for undetected prediabetes and diabetes. The FINDRISC cut-off value of 10 to identify both prediabetes and diabetes had sensitivity of 84% and specificity of 61%. Conclusions FINDRISC is a feasible, non-invasive and useful tool for identifying subjects at risk for undetected diabetes and prediabetes. Laboratory screening should be performed in subjects with FINDRISC higher than 10.
The aim of this study was to develop and examine the predictive accuracy of an index that estimates obesity risk in childhood based on perinatal factors and maternal sociodemographic characteristics. ...Analysis was conducted by using cross-sectional and retrospective data collected from a European cohort of 2775 schoolchildren and their families participating in the Feel4Diabetes-study. The cohort was randomly divided by using two-thirds of the sample for the development of the index and the remaining one third for assessing its predictive accuracy. Logistic regression analyses determined a prediction model for childhood obesity. The area under the receiver operating characteristic curve (AUC-ROC), sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated. Cut-off analysis was applied to identify the optimal value of the index score that predicts obesity with the highest possible sensitivity and specificity. Eight factors were found to be significantly associated with obesity and were included as components in the European “Childhood Obesity Risk Evaluation” (CORE) index: region of residence, maternal education, maternal pre-pregnancy weight status, gestational weight gain, maternal smoking during pregnancy, birth weight for gestational age, infant growth velocity, and exclusive breastfeeding during the first 6 months. Risk score ranged from 0 to 22 corresponding to a risk from 0.9 to 54.6%. The AUC-ROC was 0.725 with optimal cut-off ≥9 (sensitivity = 74.1%, specificity = 61.0%, PPV = 11.3%, NPV = 97.2%).
Conclusion:
The European CORE index can be used as a screening tool for the identification of infants at high-risk for becoming obese at 6–9 years. This tool could assist healthcare professionals in initiating preventive measures from the early life.
Trial registration:
The Feel4Diabetes-intervention is registered at
https://clinicaltrials.gov/
; number, CT02393872; date, March 20, 2015.
What is Known:
• As prevention of obesity should start early in life, there is a compelling rationale for the early identification of high-risk children to facilitate targeted intervention.
What is New:
• This study developed and assessed the predictive accuracy of an index for the Childhood Obesity Risk Evaluation (CORE), combining certain perinatal factors and maternal sociodemographic characteristics in a large European cohort.
• The European CORE index can be used as a screening tool for identifying infants at high-risk for becoming obese at 6–9 years and assist health professionals in initiating early prevention strategies.
Here, we review insulin management options and strategies in nonpregnant adult patients with type 1 diabetes mellitus (T1DM). Most patients with T1DM should follow a regimen of multiple daily ...injections of basal/bolus insulin, but those not meeting individual glycemic targets or those with frequent or severe hypoglycemia or pronounced dawn phenomenon should consider continuous subcutaneous insulin infusion. The latter treatment modality could also be an alternative based on patient preferences and availability of reimbursement. Continuous glucose monitoring may improve glycemic control irrespective of treatment regimen. A glycemic target of glycated hemoglobin < 7% (53 mmol/mol) is appropriate for most nonpregnant adults. Basal insulin analogues with a reduced peak profile and an extended duration of action with lower intraindividual variability relative to neutral protamine Hagedorn insulin are preferred. The clinical advantages of basal analogues compared with older basal insulins include reduced injection burden, better efficacy, lower risk of hypoglycemic episodes (especially nocturnal), and reduced weight gain. For prandial glycemic control, any rapid-acting prandial analogue (aspart, glulisine, lispro) is preferred over regular human insulin. Faster-acting insulin aspart is a relatively new option with the advantage of better postprandial glucose coverage. Frequent blood glucose measurements along with patient education on insulin dosing based on carbohydrate counting, premeal blood glucose, and anticipated physical activity is paramount, as is education on the management of blood glucose under different circumstances.
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