Insulin In People Research Articles

Effects of Plant-Based Diets on Markers of Insulin Sensitivity: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

The aim of this systematic review and meta-analysis was to examine the effects of plant-based diets on markers of insulin sensitivity in people with overweight/obesity, prediabetes, or type 2 diabetes (T2D). A systematic literature search in MEDLINE, Embase, CINAHL, and CENTRAL was conducted, and randomised controlled trials (RCTs) investigating the effect of plant-based diets (vegan, ovo-vegetarian, lacto-vegetarian, and lacto-ovo-vegetarian) for ≥14 d on markers of insulin sensitivity in adults (≥18 years) with BMI ≥ 25 kg/m2, prediabetes, or T2D were eligible. We identified eight RCTs, including 716 participants. In comparison with control diets, plant-based diets improved Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (-0.97, 95% confidence interval (CI) (-1.67, -0.27), p = 0.007) and fasting insulin (-4.13 µU/mL, 95% CI (-7.22, -1.04), p = 0.009) in people with overweight/obesity. In people with prediabetes, one study compared vegan and vegetarian diets and found no difference in HOMA-IR, or fasting insulin. One study of people with T2D reported no difference in immunoreactive insulin and metabolic glucose clearance compared with a conventional diabetes diet. In conclusion, adhering to plant-based diets for ≥14 d improved HOMA-IR and fasting insulin in people with overweight/obesity. Long-term RCTs are needed to determine whether plant-based diets can result in prolonged improvements in insulin sensitivity in people at risk of or with T2D.

Effects of Tirzepatide Versus Basal Insulins in People With Type 2 Diabetes and Different Baseline Glycemic Patterns: Post Hoc Analyses of the SURPASS-3 and SURPASS-4 Trials.

This post hoc analysis assessed change from baseline to week 52 in glycemic parameters for tirzepatide (5, 10, 15 mg) versus insulin degludec (SURPASS-3 trial) and glargine (SURPASS-4 trial) in people with type 2 diabetes and different baseline glycemic patterns, based on fasting serum glucose (FSG) and postprandial glucose (PPG) values. Participant subgroups with low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG were defined according to the median values of these measures. All tirzepatide doses and basal insulins were associated with decreased HbA1c, FSG, and PPG values from baseline to week 52 in all subgroups (P < 0.05). Within each subgroup, HbA1c and PPG decreases were greater with tirzepatide than insulin (P < 0.05). FSG decreases were generally similar. There were no differential treatment effects by FSG/PPG subgroup. In this post hoc analysis, tirzepatide was associated with superior glycemic control compared with insulin, irrespective of baseline glycemic pattern.

Efficacy and safety of basal insulins in people with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.

The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation. A comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network meta-analysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach. Of 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses. The efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern.

A Randomized Crossover Trial of Mixed Meal Tolerance Test Response in People with Type1 Diabetes on Insulin Pump Therapy and YG1699 or Dapagliflozin.

YG1699 is a novel inhibitor of sodium-glucose cotransporter 1 (SGLT1) and SGLT2. This double-blind, 3-way crossover trial compared YG1699 to dapagliflozin as an adjunct to insulin in people with type 1 diabetes (T1D) on insulin pump therapy. Treatment periods included four mixed meal tolerance tests (MMTTs) and insulin withdrawal tests per person. Nineteen adults with T1D were randomized to YG1699 10 mg, YG1699 25 mg, and dapagliflozin 10 mg once daily for 1 week in different orders. The primary end point was the difference in area under the curve (AUC) in plasma glucose (AUC0-120min) after an MMTT between treatment groups. Mean change in plasma glucose after an MMTT (AUC0-120min) was lower for YG1699 10 mg vs. dapagliflozin (89.51% of baseline vs. 102.13%, 90% confidence interval (CI) vs. dapagliflozin, -6% to -16%, P = 0.0003) and for YG1699 25 mg (84.83% vs. 102.13%, 90% CI vs. dapagliflozin -13% to -22%, P < 0.0001). At 120 minutes, mean glucose values on no treatment, dapagliflozin, YG1699 10 mg, and YG1699 25 mg were 149 (SE 7.6), 141 (SE 6.1), 128 (SE 6.9), and 115 (SE 7.8) mg/dL, respectively. Insulin dose requirements were lower for YG1699 10 mg and 25 mg vs. dapagliflozin for bolus insulin, and for YG1699 10 mg vs. dapagliflozin for total daily insulin. Safety profiles were similar between treatment groups. YG1699 reduced post-prandial glucose more than dapagliflozin in people with T1D on insulin pump therapy. The results were consistent with dual SGLT1/SGLT2 inhibition by YG1699.

Personalized Prediction of Change in Fasting Blood Glucose Following Basal Insulin Adjustment in People With Type 2 Diabetes: A Proof-of-Concept Study.

For people with type 2 diabetes treated with basal insulin, suboptimal glycemic control due to clinical inertia is a common issue. Determining the optimal basal insulin dose can be difficult, as it varies between individuals. Thus, insulin titration can be slow and cautious which may lead to treatment fatigue and non-adherence. A model that predicts changes in fasting blood glucose (FBG) after adjusting basal insulin dose may lead to more optimal titration, reducing some of these challenges. To predict the change in FBG following adjustment of basal insulin in people with type 2 diabetes using a machine learning framework. A multiple linear regression model was developed based on 786 adults with type 2 diabetes. Data were divided into training (80%) and testing (20%) sets using a ranking approach. Forward feature selection and fivefold cross-validation were used to select features. Participants had a mean age of approximately 59 years, a mean duration of diabetes of 12 years, and a mean HbA1c at screening of 65 mmol/mol (8.1%). Chosen features were FBG at week 2, basal insulin dose adjustment from week 2 to 7, trial site, hemoglobin level, and alkaline phosphatase level. The model achieved a relative absolute error of 0.67, a Pearson correlation coefficient of 0.74, and a coefficient of determination of 0.55. A model using FBG, insulin doses, and blood samples can predict a five-week change in FBG after adjusting the basal insulin dose in people with type 2 diabetes. Implementation of such a model can potentially help optimize titration and improve glycemic control.

Faktor-Faktor yang Berhubungan dengan Kejadian Diabetes Melitus (DM) di Desa Kubah Sentang Kecamatan Pantai Labu

Analyze the risk factors associated with the incidence of Diabetes Mellitus in the village of Kubah Sentang, Pantai Labu subdistrict. This type of research is quantitative descriptive with a cross sectional research design. The sample in this study were all respondents who were diagnosed with Diabetes Mellitus. Consists of a case sample of 30 people. The factors associated with the incidence of diabetes mellitus are gender, education and hypertension with the incidence of Diabetes Mellitus in residents in the village of Kubah Sentang, Pantai Labu District. The factors that are not related to the incidence of diabetes mellitus are smoking and obesity which have no association with the incidence of DM in the village of Dome Sentang. Occupational status and physical relationships are factors that can affect the risk of diabetes mellitus in Kubah Sentang Village, Pantai Labu District. Physical activity such as exercise is an important part of health in terms of disease prevention. Exercise habits do not greatly affect the decrease in blood sugar but can increase glucose oxidation which can reduce insulin in people with diabetes mellitus. Good exercise will be useful in regulating blood glucose levels in people with diabetes mellitus which will affect the control of blood sugar levels.

Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes

Once-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes. To evaluate the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes. Randomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any noninsulin glucose-lowering agents with hemoglobin A1c (HbA1c) of 7%-11% (53-97 mmol/mol). Participants were randomly assigned in a 1:1 ratio to receive either once-weekly icodec and once-daily placebo (icodec group; n = 294) or once-daily degludec and once-weekly placebo (degludec group; n = 294). The primary end point was change in HbA1c from baseline to week 26 (noninferiority margin, 0.3% percentage points). Secondary end points included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, body weight change from baseline to week 26, and number of level 2 (clinically significant; glucose level <54 mg/dL) and level 3 (severe; requiring external assistance for recovery) hypoglycemic episodes. Among 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. Mean HbA1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the icodec group and from 8.5% (observed) to 7.2% (estimated) in the degludec group (estimated treatment difference [ETD], -0.2 [95% CI, -0.3 to -0.1] percentage points), confirming noninferiority (P < .001) and superiority (P = .002). There were no significant differences between the icodec and degludec groups for fasting plasma glucose change from baseline to week 26 (ETD, 0 [95% CI, -6 to 5] mg/dL; P = .90), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs 2.3 kg; ETD, 0.46 [95% CI, -0.19 to 1.10] kg; P = .17). Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than the degludec group from week 0 to 31 (0.31 vs 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs 0.12 events per patient-year exposure; P = .01). Among people with insulin-naive type 2 diabetes, once-weekly icodec demonstrated superior HbA1c reduction to once-daily degludec after 26 weeks of treatment, with no difference in weight change and a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient-year exposure in both groups. ClinicalTrials.gov Identifier: NCT04795531.

772-P: Tirzepatide vs. Basal Insulins in People with T2D and Different Baseline Glycemic Patterns—Post Hoc Analyses of the SURPASS-3 and -4 Trials

While basal insulins act primarily by reducing fasting serum glucose (FSG), the once-weekly GIP/GLP-1 receptor agonist tirzepatide targets both FSG and postprandial glucose (PPG). This post-hoc analysis assessed the efficacy of tirzepatide vs insulin degludec (SURPASS-3) and glargine (SURPASS-4) in people with T2D and different baseline glycemic patterns. We assessed change from baseline to Week 52 in HbA1c, FSG, and PPG across subgroup categories in participants on assigned treatment without rescue medication (efficacy estimand) using mixed-model repeated measures. Four subgroups were defined by different combinations of FSG and PPG (low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, high FSG/high PPG). Low and high FSG and PPG were split based on median values of these parameters in SURPASS-3 (162 and 187 mg/dL) and -4 (164 and 197 mg/dL). While reductions in FSG were generally similar between tirzepatide and the basal insulins in both studies, decreases in PPG were greater with tirzepatide in all subgroups. This resulted in greater HbA1c reductions with tirzepatide vs basal insulin in all subgroups. The extent of reduction in FSG, PPG, and HbA1c in each subgroup was related to baseline values of these parameters. These data support previous observations of superior glycemic control with TZP compared with basal insulin, irrespective of baseline FSG and PPG levels. Disclosure F.Giorgino: Advisory Panel; Boehringer-Ingelheim, Amarin Corporation, Medtronic, Roche Diabetes Care, Sanofi, Bayer Inc., Novo Nordisk, Consultant; Novo Nordisk, Lilly, Research Support; Lilly, Roche Diabetes Care, AlfaSigma, Speaker's Bureau; Abbott, Boehringer-Ingelheim, Lilly, Sanofi, Medscape. D.R.Franco: Advisory Panel; Abbott, Eli Lilly and Company, Medtronic, Speaker's Bureau; Eli Lilly and Company, Boehringer Ingelheim and Eli Lilly Alliance, Medtronic, Sanofi, AstraZeneca, Roche Diabetes Care, Abbott Diabetes. C.Nicolay: Employee; Eli Lilly and Company. A.Hemmingway: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Á.Rodríguez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. R.Wiese: Employee; Eli Lilly and Company. Funding Eli Lilly and Company

342-OR: The Impact of Insulin Secretion and Insulin Sensitivity on Cognition in Adults with Prediabetes—The Diabetes Prevention Program Outcomes Study (DPPOS)

Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant of dysglycemia, impaired insulin sensitivity (ISens) or insulin secretion (ISecr), or both, contributes to poorer cognitive function is not established. Among 1,054 adults with prediabetes (PreD) from the DPPOS, who did not develop diabetes, we investigated the relationship between ISecr, ISens and cognitive function, hypothesizing that lower ISens and/or lower ISecr is associated with worse cognition. Early ISecr was estimated by the mean insulinogenic index (IGI; pmol/mmol) from repeated annual oral glucose tolerance tests and ISens was estimated by the mean 1/fasting insulin from repeated fasting blood draws. ISecr and ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and processing speed (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Separate linear regression models were run for each cognitive outcome. Models included both mean ISecr and mean ISens as the main predictor variables and were adjusted for demographic, lifestyle, cardiovascular factors, and medications. Contrary to our hypothesis and to prior studies, higher mean ISecr was associated with poorer performance on the DSST (-0.74 points per SD increase in IGI, 95% CI: -1.43, -0.05; p=0.03). Mean ISens was not associated with DSST, nor were mean ISecr or mean ISens associated with SEVLT. These results suggest that higher insulin secretion in people with longstanding PreD may negatively impact processing speed, a critical component of executive control. This relationship could reflect a compensatory response of insulin in people with worsening metabolic dysregulation, who may also have poorer cognition. Further study is needed to replicate these findings and to understand the role of insulin in cognitive function. Disclosure A. Shapiro: None. A.H. Tjaden: None. S. Edelstein: None. S.E. Kahn: Advisory Panel; Anji Pharmaceuticals, Bayer Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck &amp; Co., Inc. Other Relationship; Novo Nordisk. P. Srikanthan: None. W.C. Knowler: None. E.M. Venditti: None. S. Golden: Advisory Panel; Abbott Diabetes, Medtronic. O. Carmichael: Research Support; Eli Lilly and Company. Advisory Panel; Novo Nordisk. Research Support; Nestlé Health Science. K.M. Gadde: Research Support; BioKier, Inc., National Institute of Diabetes and Digestive and Kidney Diseases. J.A. Luchsinger: Consultant; Merck KGaA. Other Relationship; Wolters Kluwer Health. D. Research Group: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (UDK048489, UDK048339, UDK048377, UDK048349, UDK048381, UDK048468, UDK048434, UDK048485, UDK048375, UDK048514, UDK048437, UDK048413, UDK048411, UDK048406, UDK048380, UDK048397, UDK048412, UDK048404, UDK048387, UDK048407, UDK048443, UDK048400)

Real-World Effects of Second-Generation Versus Earlier Intermediate/Basal Insulin Analogues on Rates of Hypoglycemia in Adults with Type 1 and 2 Diabetes (iNPHORM, US).

Second-generation basal insulin analogues have been shown to reduce hypoglycemia in several trials and observational studies of select populations; however, it remains unclear whether these results persist in real-world settings. Using self-reported hypoglycemia events, we assessed whether second-generation basal insulin analogues reduce rates of hypoglycemia events (non-severe/severe; overall/daytime/nocturnal) compared to earlier intermediate/basal insulin analogues among people with insulin-treated type 1 or 2 diabetes. We used prospectively collected data from the Investigating Novel Predictions of Hypoglycemia Occurrence Using Real-World Models (iNPHORM) panel survey. This US-wide, 1-year internet-based survey assessed hypoglycemia experiences and related sociodemographic and clinical characteristics of people with diabetes (February 2020-March 2021). We estimated population-average rate ratios for hypoglycemia comparing second-generation to earlier intermediate/basal insulin analogues using negative binomial regression, adjusting for confounders. Within-person variability of repeated observations was addressed with generalized estimating equations. Among iNPHORM participants with complete data, N = 413 used an intermediate/basal insulin analogue for ≥ 1month during follow-up. After adjusting for baseline and time-updated confounders, average second-generation basal insulin analogue users experienced a 19% (95% CI 3-32%, p = 0.02) lower rate of overall non-severe hypoglycemia and 43% (95% CI 26-56%, p < 0.001) a lower rate of nocturnal non-severe hypoglycemia compared to earlier intermediate/basal insulin users. Overall severe hypoglycemia rates were similar among second-generation and earlier intermediate/basal insulin users (p = 0.35); however, the rate of severe nocturnal hypoglycemia was reduced by 44% (95% CI 10-65%, p = 0.02) among second-generation insulin users compared to earlier intermediate/basal insulin users. Our real-world results suggest second-generation basal insulin analogues reduce rates of hypoglycemia, especially nocturnal non-severe and severe events. Whenever possible and feasible, clinicians should prioritize prescribing these agents over first-generation basal or intermediate insulin in people with type 1 and 2 diabetes.

Pharmacokinetic and pharmacodynamic properties of the novel basal insulin Fc (insulin efsitora alfa), an insulin fusion protein in development for once-weekly dosing for the treatment of patients with diabetes.

To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of basal insulin Fc (BIF; LY3209590), a fusion protein combining a novel single-chain insulin variant together with human IgG2 Fc domain, following single and multiple once-weekly BIF administration. The single ascending dose, 15-day study assessed four BIF doses (5-35 mg) in healthy participants and people with type 2 diabetes (T2D). In the 6-week multiple ascending dose study, people with T2D, previously treated with basal insulin, received insulin glargine daily or a one-time loading dose of BIF followed by 5 weeks of once-weekly dosing (1-10mg). Safety, tolerability and PK and glucose PD were examined. Mean ages of people with T2D (N= 57) and healthy participants (N= 16) in the single-dose study were 58.4 and 35.8 years, respectively; mean body mass index values were 29.5 and 26.1kg/m2 . BIF had a PK half-life of approximately 17 days, which led to a sustained, dose-dependent decrease in fasting blood glucose for 5 days or longer. No severe hypoglycaemia was observed. The 6-week ascending dose study included 33 people with T2D aged 40-69 years. BIF showed a low peak-to-trough ratio of 1.14 after the last dose at week 6 (steady state). Over 6 weeks, BIF seven-point glucose profiles remained constant and were similar to insulin glargine. Rates and duration of BIF hypoglycaemic events were similar to insulin glargine. BIF was well tolerated and the PK/PD profile enabled once-weekly dosing with minimal variation in exposure in a treatment interval of 1week. The findings suggest BIF is suitable for further development as a weekly basal insulin in people with diabetes.

Evaluation of a Digital Health Tool for Titration of Basal Insulin in People With Type 2 Diabetes: Rationale and Design of a Randomized Controlled Trial.

Optimal insulin titration is essential in helping people with type 2 diabetes mellitus (T2DM) to achieve adequate glycemic control. Barriers of people with diabetes to implementation of titration include lack of self-efficiency and self-management skills, increased diabetes-related distress, low treatment satisfaction, poor well-being, as well as concerns about hypoglycemia and insulin overdose. My Dose Coach is a digital health tool for optimizing titration of basal insulin that combines a smartphone app for patients with T2DM and a Web portal for healthcare professionals. This is a prospective, open-label, multicenter, randomized controlled parallel study conducted in approximately 50 centers in Germany that are specialized in the treatment of diabetes. Patients in the intervention group will use the titration app and will be registered on the Web portal by their treating physician. Control group patients will continue their current basal insulin titration without using the app. The primary outcome is the mean change in HbA1c levels at the 12-week follow-up. The secondary outcome measures include patient-reported outcomes such as diabetes-related distress, self-management, empowerment, self-efficacy, treatment satisfaction, and psychological well-being as well as fasting blood glucose values. This digital health tool has been previously implemented in several independent pilot studies. The findings from this multicenter randomized controlled trial can provide further evidence supporting the effectiveness of this tool in patients with T2DM and serve as a basis for its clinical integration. German Register for Clinical Studies-DRKS-ID: DRKS00024861.

The barriers and facilitators to managing diabetes with insulin in adults with intellectual disabilities: A systemised review of the literature.

People with intellectual disabilities are more likely to have diabetes and develop complications from it. Diabetes management is complex and insulin treatment in particular, people with intellectual disabilities may require additional support that is not always available. This review aimed to identify barriers and facilitators to managing diabetes with insulin in adults with intellectual disabilities. Patient and public involvement (PPI) was integral to the development of the research question. A systemised review was conducted across CINAHL, the British Nursing Index and MEDLINE. PRISMA guidelines were followed. Narrative synthesis of the evidence was undertaken. Barriers and facilitators to managing diabetes with insulin in people with intellectual disabilities were identified related to the individual, other people participating in their care, and broader environmental and social factors. People with intellectual disabilities who use insulin, require reasonable adjustments to education, support, and a person-centred approach to facilitate supported self-management. More training for their supporters is needed and further inclusive research with PPI is recommended.

Twenty Years of Insulin Gla-100: A Systematic Evaluation of Its Efficacy and Safety in Type 2 Diabetes Mellitus.

IntroductionThis systematic review aims to present the current evidence base with respect to the initiation and intensification of insulin therapy with glargine 100 U/mL (Gla-100) compared to other insulins in people with type 2 diabetes mellitus (T2DM).MethodsA systematic literature search of PubMed (MEDLINE), EMBASE, and the Cochrane Central Register of controlled clinical trials databases was performed to identify studies published up to September 30, 2020 that compared the effects of Gla-100 to that of other insulin regimens in people with T2DM. Relevant information pertaining to the predefined outcomes of interest was extracted. Glycated hemoglobin (HbA1c) change and response rates along with overall hypoglycemia incidence were the primary efficacy and safety outcomes of interest.ResultsSeventy-nine studies (63 interventional and 16 non-interventional) in which Gla-100 was either initiated in previously insulin-naïve patients (n = 57) or used in an intensified regimen (n = 22) were identified and evaluated. In insulin-naïve patients, most studies demonstrated that Gla-100 was significantly better compared with premixed insulins and similar compared with neutral protamine Hagedorn (NPH) insulin, second-generation basal insulins, co-formulations, and other first-generation basal insulins in terms of the primary efficacy parameters. Overall hypoglycemia risk with Gla-100 was significantly lower compared with NPH, premixed, coformulation, and other first-generation basal insulins and significantly higher compared with second-generation basal insulins. In studies with intensified regimens, efficacy outcomes with Gla-100 were significantly better compared with insulin detemir (IDet); similar compared with NPH, second-generation basal insulins, co-formulations; and with premixed insulins. In these studies, overall hypoglycemia risk with Gla-100 was significantly lower compared with IDet and comparable to NPH, premixed insulins, co-formulations, and second-generation basal insulins. In addition, most intensification studies also revealed a significantly lower risk of nocturnal hypoglycemia with Gla-100–based regimens versus NPH and premixed insulins and a significantly greater risk compared to second-generation basal insulins.ConclusionsThe evidence presented in this review suggests that Gla-100 is an effective option for both insulin initiation and intensification strategies used in the management of T2DM.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01284-2.

Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes.

AimMultiple studies support the efficacy of combining a glucagon‐like peptide 1 receptor agonist (GLP‐1RA) with basal insulin in people with type 2 diabetes inadequately controlled on dual/triple oral therapy. Fixed‐ratio combinations of basal insulin + GLP‐1RA represent a further advance to facilitate management. We assessed the impact of fixed‐ratio combination basal insulin + GLP‐1RA treatment on β‐cell function.Materials and MethodsWe analysed data from 351 participants in the LixiLan‐G trial (NCT02787551) randomized to receive iGlarLixi (insulin glargine 100 U/ml + lixisenatide) or to continue daily/weekly GLP‐1RA, both on top of metformin. Participants received a 2‐h meal tolerance test before randomization and at study end (26 weeks), with timed plasma glucose and C‐peptide determinations. β‐cell function parameters were resolved using mathematical modelling.ResultsIn the GLP‐1RA group (n = 162), both body weight and glycated haemoglobin decreased at week 26, yet none of the insulin secretion/β‐cell function parameters changed significantly. In contrast, in the iGlarLixi group (n = 189), glycated haemoglobin decreased significantly more than in the GLP‐1RA group (p < .0001) despite an increase in body weight (+1.7 ± 3.9 kg, p < .0001). Fasting and stimulated insulin secretion decreased at Week 26 (both p < .0001 vs. GLP‐1RA), while β‐cell glucose sensitivity increased by a median 35% (p = .0032 vs. GLP‐1RA). The incremental meal tolerance test glucose area showed a larger reduction with iGlarLixi versus GLP‐1RA (p < .0001).ConclusionsIn people with type 2 diabetes on metformin, 26‐week treatment with iGlarLixi resulted in a marked improvement in β‐cell function concomitant with sparing of endogenous insulin release and a reduction in meal absorption.

Real-world Evidence of Efficacy and Safety of SGLT2 Inhibitors as Adjunctive Therapy in Adults With Type 1 Diabetes: A European Two-Center Experience

To evaluate real-world efficacy and safety of sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in combination with insulin in people with type 1 diabetes. We conducted a retrospective cohort European two-center study. Data on demographics, HbA1c, weight, insulin use, renal function, and adverse events were collected for 199 adults with type 1 diabetes who initiated a SGLT2i adjunct to insulin. Subgroup analyses were performed to identify who benefited most and who was more at risk for adverse events. Overall, significant reductions in mean HbA1c (-0.5%), weight (-2.9 kg), and daily insulin (-8.5%) were achieved after 12 months. The greatest reduction in HbA1c was obtained in individuals with baseline HbA1c >8% (-0.7% [64 mmol/mol]). The most weight loss was observed in subjects with BMI >27 kg/m2 (-3.5 kg). Individuals with baseline estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 showed an increase in eGFR (4.5 mL/min/1.73 m2), whereas those with urinary albumin-to-creatinine ratio (UACR) >15 mg/g showed a decrease in UACR (-16.6 mg/g). Fifty-seven individuals (28.6%) reported adverse events: 45 with genital infections (22.6%), 5 ketosis episodes (2.5%), and 7 diabetic ketoacidosis (DKA) (3.5%). No severe hypoglycemia events were reported. Our real-world data on SGLT2i showed promising results in reductions in HbA1c, weight, and insulin requirements in type 1 diabetes. Benefits were more pronounced in individuals with higher baseline HbA1c and BMI. DKA remained a major concern, despite educational measures. Further real-life evidence is still required for evaluation of SGLT2i longer-term effects and their impact on reno-cardiovascular outcomes.

Effects of prebiotics on postprandial GLP-1, GLP-2 and glucose regulation in patients with type 2 diabetes: A randomised, double-blind, placebo-controlled crossover trial.

We aimed to investigate the effect of prebiotic inulin-type fructans (ITF) versus a control supplement on postprandial levels of glucagon-like peptide-1 and -2 (GLP-1 and -2), glucose and insulin in people with type 2 diabetes. Adult men and women with type 2 diabetes were randomised in a double-blind, placebo-controlled crossover study. The study participants received 16g/d ITF and 16g/d control supplement (maltodextrin) for 6weeks each in two phases separated by a 4-week washout. A standardised mixed-meal test was performed before and after each intake period. The primary end point was changes in the GLP-1 response, and secondary end points were GLP-2, glucose and insulin responses. Data were analysed using mixed-model analysis. A total of 29 participants were included in the study. Differences between and within the two treatments in estimated area under the curves were not significant. Yet, the predicted means for meal-induced GLP-1 response in plasma showed a 4.8% decline after the prebiotic treatment and an 8.6% increase after the control treatment (difference in changes between the treatments, p<0.001). Fasting or postprandial glucose, insulin or GLP-2levels were not changed. Our findings do not support that ITF improve incretin responses or glucose regulations in this population. Clinicaltrials.gov (NCT02569684).

Attitudes and beliefs of South African primary healthcare practitioners on initiating insulin in people with type 2 diabetes: Findings from the Tshwane Insulin Project (TIP)

AimsTo investigate the attitudes and beliefs of primary healthcare practitioners (HCPs) towards initiating insulin therapy for people with type 2 diabetes (T2D) in South Africa. MethodsA cross-sectional survey was conducted amongst HCPs from 23 clinics. The nurses’ questionnaire was administered by research nurses while doctors completed an online version about their attitudes, beliefs and perceived barriers to initiating insulin. ResultsOf the 73 HCPs surveyed, 68% were nurses and 84% were women. Only 24% of HCPs believed that most patients would eventually need to initiate insulin regardless of their adherence to treatment regimens and 86% preferred to delay insulin therapy. Doctors were reluctant to initiate insulin, citing patient-related reasons such as low socio-economic level (41%), inability to refrigerate insulin (77%) and inability to self-monitor blood glucose (55%). Doctors mentioned that patient behaviour including not adhering to treatment regimen and appointments (91%) and reluctance to start insulin therapy (82%) influenced their prescription practices. Doctors mentioned that health system factors, including the pressure to see patients quickly (68%) and lack of continuity of care (64%) were barriers to initiating insulin. ConclusionsOptimising insulin therapy in primary care requires health system changes including promoting person-centred care and continuing training for HCPs.

(Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus.

(Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus.

Glucose Response to Fast- and Long-Acting Insulin in People with Type 2 Diabetes

In type 2 diabetes (T2D), injections with long-acting insulin can become necessary to regulate blood glucose and avoid long-term complications. However, finding a safe and effective insulin dose, a process known as titration, is both challenging and time demanding. In this paper, we propose a new method for safe and rapid identification of a personalized insulin dose with long-acting insulin through short-term use of fast-acting insulin in an artificial pancreas (AP). To illustrate this novel concept, we simulate our method by modelling the glucose response to fast-and long-acting insulin in people with T2D. We apply a simple control-algorithm for the AP to adjust the insulin infusion rate during fasting periods. In this case-study, we simulate an insulin naïve T2D patient on AP treatment for one week, gradually adjusting the insulin infusion rate. After one week, we convert the insulin infusion rate, unit-to-unit, to a daily injection of long-acting insulin. We compare our method to titration with the standard of care 2-0-2 algorithm. Our simulations indicate that we can reduce the titration period from five weeks to a single week, whilst easing the burden on the patient.