ABSTRACT
BACKGROUND: In this multicenter study, performance of a novel continuous glucose monitoring (CGM) system was evaluated. METHODS: Adult participants with diabetes were included in the study. They each wore three sensors of the CGM system on the upper arms for up to 14 days. During four in-clinic visits, frequent comparison measurements with capillary blood glucose (BG) samples were performed. The primary endpoint was the 20/20 agreement rate (AR): the percentage of CGM readings within ±20 mg/dL (at BG values <100 mg/dL) or ±20% (at BG values ≥100 mg/dL) of the comparator. Further evaluations included mean absolute relative difference (MARD) and 20/20 AR in different BG ranges and across the wear time. RESULTS: Data from 48 participants and 139 sensors were analyzed. During in-clinic sessions the 20/20 AR was 90.5% and the MARD was 9.2%. For BG ranges <70, 70-180, and >180 mg/dL, 20/20 AR was 94.3%, 89.0%, and 92.5%, respectively. At the beginning, middle, and end of sensor wear time, 20/20 AR was 92.8%, 91.5%, and 85.9%, respectively. The 14-day survival probability was 82.4%. Pain and bleeding after sensor insertion were within the expected range. Based on the study outcome, the use of the device is regarded as safe. CONCLUSIONS: The system showed a good performance compared to capillary BG measurements. This level of accuracy could be shown over the entire measurement range, especially in the low glycemic range, and the whole wear time of the sensors. The results of this study are supporting a non-adjunctive use of the device.
ABSTRACT
INTRODRODUCTION: Obesity and its associated metabolic conditions have become a significant global health problem in recent years, with many people living with obesity fulfilling criteria for pharmacological treatment. The development of the glucagon-like peptide-1 receptor agonists for chronic weight management has triggered new interest in the incretins and other hormones as targets for obesity, and investigations into dual and triple co-agonists. METHODS: The objective of this narrative review was to summarize the available data on approved and emerging incretin-based agents for the treatment of obesity. RESULTS: In clinical trials of currently available agents in people with overweight or obesity, weight loss of between 6% and 21% of baseline body weight has been observed, with between 23% and 94% of participants achieving 10% or higher weight loss, depending on the study and the agent used. Favourable outcomes have also been seen with regard to cardiovascular risk and outcomes, diabetes prevention, metabolic dysfunction-associated steatotic liver disease/steatohepatitis and prevention of weight regain after metabolic surgery. Limitations associated with these agents include high costs, the potential for weight regain once treatment is stopped, the potential loss of lean body mass and gastrointestinal adverse events; potential issues with respect to gallbladder and biliary diseases require further investigation. CONCLUSIONS: Many dual and triple co-agonists are still in development, and more data are needed to assess the efficacy, safety and tolerability of these emerging therapies versus the established incretin-based therapies; however, data are promising, and further results are eagerly awaited.
ABSTRACT
Purpose: This observational trial was performed to evaluate liver parameters in overweight or obese subjects in the context of insulin resistance and glucose control over time. Subjects/Methods: Insulin resistance, glucose control and several parameters for liver integrity were monitored in 177 overweight (BMI > 28 kg/m2) subjects over a mean of 30 months. Volunteers were categorized according to insulin resistance (HOMAIR score) and glucose control in subjects with normal glucose control (NGT), impaired glucose control (IGT), or diabetes mellitus type 2 (T2DM). Liver fat and fibrosis were evaluated by sonographic elastography (FibroScan®) and clinical scores, such as the AST/ALT ratio, fatty liver index (FLI), and NAFLD fibrosis score (NFS). Results: Liver fat fraction as estimated by the controlled attenuation parameter (CAP), and the FLI were significantly higher in subjects with T2DM compared to IGT and NGT. While fasting insulin levels and the HOMAIR score continuously increased over time, no change in CAP or FLI occurred during follow up. CAP was correlated with FLI (r = 0.50; p < 0.0001) and the HOMAIR score (r = 0.32; p < 0.0001). An inverse correlation was observed between serum adiponectin levels and FLI (r = -0.37; p < 0.0001), the HOMAIR score (r = -0.19; p < 0.001, and CAP (r = -0.15; p < 0.01). Conclusions: In subjects with a BMI ≥ 28 kg/m2, liver fat fraction is significantly elevated in those with T2DM compared to IGT or NGT. Liver fat fraction is associated with deteriorating insulin sensitivity and loss of glucose control. Despite a continuous increase in insulin resistance, no change in liver fat content or stiffness occurred over 30 months.
ABSTRACT
The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Diabetes Mellitus , Heart Failure , Renal Insufficiency, Chronic , Humans , Heart Failure/complications , Blood Glucose Self-Monitoring , Stroke Volume , Blood Glucose , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Obesity/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Diabetes Mellitus/drug therapy , Kidney , Diabetes Mellitus, Type 2/drug therapyABSTRACT
Changes in the pharmacokinetic and resulting pharmacodynamic properties of drugs are common in many chronic liver diseases, leading to adverse effects, drug interactions and increased risk of over- or underdosing of medications. Structural and functional hepatic impairment can have major effects on drug metabolism and transport. This review summarizes research on the functional changes in phase I and II metabolic enzymes and in transport proteins in patients with metabolic diseases such as type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis and cirrhosis, providing a clinical perspective on how these changes affect drug uptake and metabolism. Generally, a decrease in expression and/or activity of many enzymes of the cytochrome P450 family (e.g. CYP2E1 and CYP3A4), and of influx and efflux transporters (e.g. organic anion-transporting polypeptide [OATP]1B1, OATP2B1, OAT2 and bile salt export pump), has been recently documented in patients with liver disease. Decreased enzyme levels often correlate with increased severity of chronic liver disease. In subjects with hepatic impairment, there is potential for strong alterations of drug pharmacokinetics due to reduced absorption, increased volume of distribution, metabolism and extraction. Due to the altered pharmacokinetics, specific drug-drug interactions are also a potential issue to consider in patients with liver disease. Given the huge burden of liver disease in western societies, there is a need to improve awareness among all healthcare professionals and patients with liver disease to ensure appropriate drug prescriptions.
Subject(s)
Diabetes Mellitus, Type 2 , Liver Diseases , Organic Anion Transporters , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Liver/metabolism , Metabolic Clearance Rate , Drug Interactions , Membrane Transport Proteins/metabolism , Organic Anion Transporters/metabolism , Organic Anion Transporters/pharmacology , Liver Diseases/metabolismABSTRACT
Ultra-rapid-acting insulin analogs (URAA) are a further development and refinement of rapid-acting insulin analogs. Because of their adapted formulation, URAA provide an even faster pharmacokinetics and thus an accelerated onset of insulin action than conventional rapid-acting insulin analogs, allowing for a more physiologic delivery of exogenously applied insulin. Clinical trials have confirmed the superiority of URAA in controlling postprandial glucose excursions, with a safety profile that is comparable to the rapid-acting insulins. Consequently, many individuals with diabetes mellitus may benefit from URAA in terms of prandial glycemic control. Unfortunately, there are only few available recommendations from authoritative sources for use of URAA in clinical practice. Therefore, this expert consensus report aims to define populations of people with diabetes mellitus for whom URAA may be beneficial and to provide health care professionals with concrete, practical recommendations on how best to use URAA in this context.
ABSTRACT
The 8th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Kidney, and Glycemic Outcomes was held virtually on November 10-12, 2022. Following the tradition of previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed outcomes trials as well as key trials important to the cardiovascular (CV) field. This year's focus was on the results of the DELIVER, EMPA-KIDNEY and SURMOUNT-1 trials and their implications for the treatment of heart failure (HF) and chronic kidney disease (CKD) with sodium-glucose cotransporter-2 (SGLT2) inhibitors and obesity with glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. A broad audience of primary care physicians, diabetologists, endocrinologists, cardiologists, and nephrologists participated online in discussions on new consensus recommendations and guideline updates on type 2 diabetes (T2D) and CKD management, overcoming clinical inertia, glycemic markers, continuous glucose monitoring (CGM), novel insulin preparations, combination therapy, and reclassification of T2D. The impact of cardiovascular outcomes on the design of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) trials, as well as the impact of real-world evidence (RWE) studies on the confirmation of CVOT outcomes and clinical trial design, were also intensively discussed. The 9th Cardiovascular Outcome Trial Summit will be held virtually on November 23-24, 2023 ( http://www.cvot.org ).
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Humans , Blood Glucose , Blood Glucose Self-Monitoring , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/therapeutic use , Kidney , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/epidemiologyABSTRACT
BACKGROUND: Obesity is a complex disease associated with multiple concurrent complications, and the coordinated targeting of multiple pathways in pharmacological treatment may improve weight loss outcomes. During synthesis, ghrelin is converted from the 'inactive' unacylated ghrelin (UAG) to the active acylated ghrelin (AG) by the enzyme ghrelin-O-acyltransferase (GOAT), stimulating appetite and food intake. AIMS: To report the results of two Phase I studies investigating single rising doses (SRDs) or multiple rising doses (MRDs) of the novel oral GOAT inhibitor BI 1356225 versus placebo in male and postmenopausal/sterilised female subjects with overweight or obesity. METHODS: The SRD study investigated single doses of BI 1356225 (0.1-20.0 mg) in healthy male subjects with a BMI of 18.5-29.9 kg/m2 (SRD cohort) and assessed doses of 2.5 mg BI 1356225 under fed and fasted conditions (bioavailability [BA] cohort). The MRD study investigated multiple doses of BI 1356225 (0.2, 1.0, 2.5 or 10.0 mg) or 5.0 mg BI 1356225 with a single dose of midazolam and celecoxib (drug-drug interaction part) over 28 days in adults with a BMI of 27.0-39.9 kg/m2. RESULTS: Sixty-five subjects were treated in the SRD study. Drug-related adverse events (AEs) were reported for five subjects (9.1 %) in the SRD cohort and two subjects (20.0 %) in the BA cohort, with the most frequent being headache (SRD: n = 4, 9.8 %; BA: n = 1, 10.0 %). In the MRD study, two (2.3 %) of the 87 subjects treated discontinued treatment because of AEs. Drug-related AEs were reported for 18 subjects (20.7 %), did not increase with dose and were most frequently reported as headache (n = 5, 5.7 %) and gastrointestinal disorders (n = 5, 5.7 %). In both studies, exposure parameters (area under the concentration-time curve [AUC] and maximum plasma concentration [Cmax]) of BI 1356225 increased across dose groups, although this was less than dose-proportional across the entire dose range. In the BA cohort of the SRD study, AUC0-∞ was slightly increased and Cmax slightly decreased in fed versus fasted conditions, with fed/fasted ratios (90 % CI) of 101.10 % (92.42, 110.60) and 91.67 % (78.50, 107.05), respectively. In both studies, AG concentrations and the AG/UAG ratio were dose-dependently decreased after BI 1356225 treatment from baseline versus placebo. In the MRD study, UAG concentrations were increased from baseline, but not dose-dependently. No differences were observed in bodyweight, appetite, food cravings, ad libitum food uptake or obesity-related biomarkers after 28 days of treatment with BI 1356225. CONCLUSIONS: Treatment with SRDs and MRDs of BI 1356225 was well tolerated by healthy males and subjects with overweight/obesity. BI 1356225 treatment over 28 days reduced AG concentrations and the AG/UAG ratio by >80 %, but no effect was seen on bodyweight, hunger/satiety, control of eating or energy intake. Although, at 4 weeks, the MRD study was fairly short, a reduction in bodyweight would be expected to be evident by this time, suggesting that a reduction of AG via a GOAT inhibitor is not sufficient to induce clinically relevant bodyweight loss.
Subject(s)
Acyltransferases , Obesity , Overweight , Female , Male , Acyltransferases/antagonists & inhibitors , Area Under Curve , Body Weight , Double-Blind Method , Ghrelin , Headache/chemically induced , Obesity/drug therapy , Overweight/drug therapy , HumansABSTRACT
BACKGROUND: A wave of expiring patents for first-generation insulin analogues has created opportunities in the global insulin market for highly similar versions of these products, biosimilar insulins. Biologics are generally large, complex molecules produced through biotechnology in a living system, such as a microorganism, plant cell, or animal cell. Since manufacturing processes of biologics vary, biosimilars cannot be exact copies of their reference product but must exhibit a high degree of functional and structural similarity. Biosimilarity is proven by analytical approaches in comparative assessments, preclinical cell-based and animal studies, as well as clinical studies in humans facilitating the accumulation of evidence across all assessments. The approval of biosimilars follows detailed regulatory pathways derived from those of their reference products and established by agencies such as the European Medicines Agency and the US Food and Drug Administration. Regulatory authorities impose requirements to ensure that biosimilars meet high standards of quality, safety, and efficacy and are highly similar to their reference product. PURPOSE: This review aims to aid clinical understanding of the high standards of development, manufacturing, and regulation of biosimilar insulins. METHODS: Recent relevant studies indexed by PubMed and regulatory documents were included. CONCLUSIONS: Driven by price competition, the emergence of biosimilar insulins may help expand global access to current insulin analogues. To maximize the impact of the advantage for falling retail costs of biosimilar insulins compared with that of reference insulins, healthcare professionals and insulin users must gain further awareness and confidence.
Subject(s)
Biosimilar Pharmaceuticals , Insulins , Animals , United States , Humans , Insulin , Insulins/therapeutic use , Insulin, Regular, Human , United States Food and Drug Administration , Drug ApprovalABSTRACT
BACKGROUND: Diabetic kidney disease (DKD), the most common cause of kidney failure and end-stage kidney disease worldwide, will develop in almost half of all people with type 2 diabetes. With the incidence of type 2 diabetes continuing to increase, early detection and management of DKD is of great clinical importance. MAIN BODY: This review provides a comprehensive clinical update for DKD in people with type 2 diabetes, with a special focus on new treatment modalities. The traditional strategies for prevention and treatment of DKD, i.e., glycemic control and blood pressure management, have only modest effects on minimizing glomerular filtration rate decline or progression to end-stage kidney disease. While cardiovascular outcome trials of SGLT-2i show a positive effect of SGLT-2i on several kidney disease-related endpoints, the effect of GLP-1 RA on kidney-disease endpoints other than reduced albuminuria remain to be established. Non-steroidal mineralocorticoid receptor antagonists also evoke cardiovascular and kidney protective effects. CONCLUSION: With these new agents and the promise of additional agents under clinical development, clinicians will be more able to personalize treatment of DKD in patients with type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Kidney Failure, Chronic , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/drug therapy , Glucagon-Like Peptide 1/therapeutic use , Humans , Mineralocorticoid Receptor Antagonists/therapeutic useABSTRACT
The 7th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Renal, and Glycemic Outcomes, was held virtually on November 18-19, 2021. Pursuing the tradition of the previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed CVOTs. This year's focus was placed on the outcomes of EMPEROR-Preserved, FIGARO-DKD, AMPLITUDE-O, SURPASS 1-5, and STEP 1-5. Trial implications for diabetes and obesity management and the impact on new treatment algorithms were highlighted for endocrinologists, diabetologists, cardiologists, nephrologists, and general practitioners. Discussions evolved from outcome trials using SGLT2 inhibitors as therapy for heart failure, to CVOTs with nonsteroidal mineralocorticoid receptor antagonists and GLP-1 receptor agonists. Furthermore, trials for glycemic and overweight/obesity management, challenges in diabetes management in COVID-19, and novel guidelines and treatment strategies were discussed.Trial registration The 8th Cardiovascular Outcome Trial Summit will be held virtually on November 10-11, 2022 ( http://www.cvot.org ).
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Blood Glucose , COVID-19 , Cardiovascular Diseases/drug therapy , Clinical Trials as Topic , Diabetes Mellitus/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Treatment OutcomeABSTRACT
The 6th Cardiovascular Outcome Trial (CVOT) Summit "Cardiovascular and Renal Outcomes 2020" was the first to be held virtually on October 29-30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA-CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed.The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18-19, 2021 ( http://www.cvot.org ).
Subject(s)
COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Clinical Trials as Topic/methods , Congresses as Topic/trends , Renal Insufficiency, Chronic/epidemiology , Research Report/trends , COVID-19/therapy , Cardiovascular Diseases/therapy , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Humans , Kidney/drug effects , Kidney/physiology , Mineralocorticoid Receptor Antagonists/administration & dosage , Renal Insufficiency, Chronic/therapy , Sodium-Glucose Transporter 2 Inhibitors/administration & dosage , Treatment OutcomeABSTRACT
Initiating insulin therapy with a basal insulin analogue has become a standard of care in the treatment of type 2 diabetes mellitus (T2DM). Despite increasing choices in pharmacological approaches, intensified glucose monitoring and improvements in quality of care, many patients do not achieve the desired level of glycaemic control. Although insulin therapy, when optimized, can help patients reach their glycaemic goals, there are barriers to treatment initiation on both the side of the patient and provider. Providers experience barriers based on their perceptions of patients' capabilities and concerns. They may lack the confidence to solve the practical problems of insulin therapy and avoid decisions they perceive as risky for their patients. In this study, we review recommendations for basal insulin initiation, focussing on glycaemic targets, titration, monitoring, and combination therapy with non-insulin anti-hyperglycaemic medications. We provide practical advice on how to address some of the key problems encountered in everyday clinical practice and give recommendations where there are gaps in knowledge or guidelines. We also discuss common challenges faced by people with T2DM, such as weight gain and hypoglycaemia, and how providers can address and overcome them.
Subject(s)
Diabetes Mellitus, Type 2 , Blood Glucose , Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 2/drug therapy , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/therapeutic use , Insulin , Insulin, Regular, HumanABSTRACT
Using mobile OCT equipment and remote ophthalmological diagnosis of n = 1538 diabetics in 17 diabetes practices in Germany, we found diabetic macular edema in 10.1% of the patients and retinal bleedings or microaneurysms in 15.6%. In 1.62% of the diabetics examined, the size of the edema was > 0.4 mm², in 7% the retinal thickness was > 300 µm and thus in need of treatment. An intravitreal anti-VEGF injection was administered prior to the examination in only 10% of the patients with diabetic macular edema. By means of mobile tele-eye consultation and remote ophthalmological diagnosis using the cloud-based patient file certified as medical device IIa, patients with diabetic macular edema were identified and informed on site quickly and definitively. The data and images were made available to all attending physicians and ophthalmic surgeons.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/therapy , Humans , Intravitreal Injections , Macular Edema/drug therapy , Macular Edema/therapy , Retina , Tomography, Optical CoherenceABSTRACT
We investigated the effect of sequential treatment escalation with dapagliflozin and saxagliptin on beta cell function in patients with T2DM insufficiently controlled on metformin monotherapy during a hyperglycaemic clamp investigation. Twenty-six patients (19 males, age 63.5±7.0 years; duration of diabetes 8.8±4.7 years; HbA1c 63.9±15.8 mmol/mol; mean±SD) were enrolled in the study. During a first treatment period (TP1) all patients received 10 mg dapagliflozin for one month, followed by the addition of 5 mg saxagliptin or placebo for another month (TP2). At baseline and at the end of each treatment period, fasting glucose and insulin levels were analysed, and a hyperglycaemic clamp with the measurement of plasma C-peptide, insulin, proinsulin, and glucagon was performed. Treatment with dapagliflozin reduced fasting glucose levels and insulin resistance (TP1). Within the hyperglycaemic clamp, C-peptide and insulin concentrations increased after the addition of dapagliflozin in TP1 (0.48±0.45 nmol*h/l; 6.24±17.9 mU*h/l) and further improved after the addition of saxagliptin in TP2 (0.38±0.34 nmol*h/l; 6.59±10.15 mU*h/l). Acute insulin response did not change after the addition of dapagliflozin (TP1), but significantly improved after the addition of saxagliptin in TP2 (0.89±0.76 mU*h/l). Both drugs improved the C-peptide/proinsulin ratio. After the addition of saxagliptin, the glucagon/insulin ratio significantly declined (TP2). Treatment escalation with dapagliflozin and saxagliptin exhibit additive effects on beta cell capacity, and improves alpha and beta cell integrity.
Subject(s)
Adamantane/analogs & derivatives , Benzhydryl Compounds/administration & dosage , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Dipeptides/administration & dosage , Glucosides/administration & dosage , Insulin-Secreting Cells/metabolism , Adamantane/administration & dosage , Aged , Double-Blind Method , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Real-time continuous glucose monitoring is associated with significant benefits for diabetes management. Implantable sensors could overcome some challenges reportedly associated with device visibility, psychosocial functioning and sensor durability. METHODS: A psychosocial assessment was conducted to determine acceptability and impact of an implantable continuous glucose monitoring (CGM) sensor as part of the PRECISE trial. Questionnaires were administered to participants comprising the Diabetes Distress Scale, the CGM impact scale, and bespoke device satisfaction. RESULTS: Fifty-one participants across the United Kingdom (n = 10) and Germany (n = 41) completed the questionnaires. Of these, 90% had T1D, 50% followed an insulin pump therapy regimen, and 45% of the participants were previous CGM users. CGM Impact Scale results show 86% (n = 44) of participants reported feeling better (14% neutral) about their diabetes control with 90% CGM naïve participants and 81% previous CGM users reporting increased confidence about their diabetes management. Furthermore, 73% (n = 37) felt more safe (27% neutral) while sleeping and 78% (n = 39) more confident (22% neutral) about avoiding serious hypoglycemia. Responses correspond with an average improvement in HbA1c from 7.51 to 7.05 ( P < .0001) over the 90 days use of the CGM. Overall, the system was rated highly on ease of use, convenience and comfort. 84% would choose to be inserted again with 93% of CGM naïve participants (86% previous CGM users) reporting minimized burden of diabetes. CONCLUSIONS: Implantable CGM devices are acceptable to users and are evaluated favorably. The considerable majority of participants (93% of first time users and 77% previous CGM users) would like to continue using the system to help manage their diabetes more effectively.
Subject(s)
Blood Glucose Self-Monitoring/instrumentation , Blood Glucose Self-Monitoring/psychology , Blood Glucose/analysis , Patient Acceptance of Health Care , Adolescent , Adult , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Female , Humans , Male , Patient Acceptance of Health Care/psychology , Surveys and QuestionnairesABSTRACT
BACKGROUND: Painful subcutaneous insulin injections may decrease treatment compliance. Improving injection comfort therefore represents a particular area of technological research in which steady progress has been made since the introduction of the insulin pen in 1985. Injection pain can be influenced by many variables, but relatively little is known about their impact. This study investigated the impact of injection volume (range 0-2250 µL), speed (range 0-800 µL/sec), and site (abdomen vs thigh) on pain sensation. METHOD: In random order, patients (n = 80) with type 1 or type 2 diabetes received 24 saline injections subcutaneously through a 27G ultra-thin-wall needle. Injections were performed in the abdomen (n = 19) and thigh (n = 5) with predefined speed-volume combinations. For each injected speed-volume combination, patients scored their pain sensation on a 100 mm visual analog scale (VAS). RESULTS: The mean pain scores for speed-volume combinations were all in the lower part (<20 mm) of the VAS, indicating zero to mild pain. Pain sensation was statistically higher ( P < .05) with the 2250 µL volume compared to other injection volumes (range 4.3-5.1 mm) and with thigh compared to abdomen injections (2.1 mm). Pain sensation did not change with increasing injection speed. Patient acceptance of the injection pain was high for all injections (range 93.7-98.7%). CONCLUSIONS: In summary, large volume and thigh injections are rated more painful, but the clinical impact of these findings is likely marginal considering the low absolute pain levels and high patient acceptance rates. Injection speed does not influence pain sensation.
Subject(s)
Injection Site Reaction/etiology , Injections, Subcutaneous/adverse effects , Pain/etiology , Abdomen , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Humans , Pain Measurement , ThighABSTRACT
BACKGROUND: Basal insulin peglispro (BIL) has a peripheral-to-hepatic distribution of action that resembles endogenous insulin and a prolonged duration of action with a flat pharmacokinetic/pharmacodynamic profile at steady state, characteristics that tend to reduce hypoglycemia risk compared to insulin glargine (GL). The primary objective was to demonstrate that clinically significant hypoglycemia (blood glucose ≤54 mg/dL [3.0 mmol/L] or symptoms of severe hypoglycemia) occurred less frequently within 84 h after a double dose (DD) of BIL than a DD of GL. METHODS: This was a randomized, double-blind, two-period crossover study in patients with type 2 diabetes (T2D) previously treated with insulin (N = 68). For the first 3 weeks of each of the two crossover periods, patients received an individualized dose of BIL or GL once nightly (stable dose for 2 weeks/period). Then, during a 7-day inpatient stay with frequent blood glucose monitoring and standardized meals, one DD of study insulin was given. Glucose was infused if blood glucose was ≤54 mg/dL (3.0 mmol/L) or for symptoms of severe hypoglycemia. RESULTS: Within 84 h after the DD, a significantly smaller proportion of patients experienced clinically significant hypoglycemia with BIL compared to GL (BIL, 6.6%; GL, 35.5%; odds ratio for BIL/GL 0.13 [95% confidence interval 0.04-0.39]; P < 0.001). Adverse event profiles were similar for the two insulins. Serum alanine aminotransferase and triglyceride levels were significantly higher with BIL versus GL. CONCLUSIONS: BIL has a markedly lower risk of hypoglycemia than GL when replicating a double-dose error in patients with T2D.