The Experts below are selected from a list of 3138 Experts worldwide ranked by ideXlab platform
David Russell-jones - One of the best experts on this subject based on the ideXlab platform.
-
Weight-sparing effect of Insulin Detemir: a consequence of central nervous system-mediated reduced energy intake?
Diabetes obesity & metabolism, 2015Co-Authors: David Russell-jones, Kjeld Hermansen, Thomas Danne, Kevin D. Niswender, K. Robertson, N. Thalange, J. R. Vasselli, B. Yildiz, H.-u. HäringAbstract:Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and Insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that Insulin Detemir, a basal Insulin analogue, exerts a unique weight‐sparing effect compared with other basal Insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to Insulin Detemir and comparator basal Insulins. The following models have been proposed: Insulin Detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that Insulin Detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter‐regulatory response to Insulin through restoration of the hepatic–peripheral Insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight‐sparing effect of Insulin Detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.
-
A comparison of Insulin Detemir and neutral protamine Hagedorn (isophane) Insulin in the treatment of diabetes: a systematic review.
Diabetes obesity & metabolism, 2013Co-Authors: Brian M. Frier, David Russell-jones, T. HeiseAbstract:The aim of this review is to summarize the clinical efficacy, tolerability and safety data of Insulin Detemir, and compare its use with that of neutral protamine Hagedorn (NPH) Insulin in randomized controlled trials in people with type 1 or type 2 diabetes. A literature search was conducted with PubMed using predefined search terms. Studies were included if they met the following criteria: randomized, controlled trial, comparison of Insulin Detemir with NPH Insulin, non-hospitalized adults aged ≥18 years with either type 1 or type 2 diabetes, and study duration of ≥12 weeks. The following types of studies were excluded: non-randomized controlled trials, studies of mixed cohorts of patients with type 1 or type 2 diabetes that did not report results separately, pharmacokinetic/pharmacodynamic studies, reviews, pooled or meta-analyses or health-economic analyses. Fourteen publications met the inclusion criteria. Nine studies in people with type 1 diabetes and three studies in people with type 2 diabetes, using Insulin Detemir in a basal-bolus regimen were included. Two studies were in people with type 2 diabetes using Insulin Detemir with oral antidiabetes medicines. In 14 studies of people with type 1 or type 2 diabetes, Insulin Detemir treatment provided similar or better glycaemic control, lower within-subject variability, similar or lower frequency of hypoglycaemia and less weight gain when compared with NPH Insulin.
-
Insulin Detemir Reduces Weight Gain As a Result of Reduced Food Intake in Patients With Type 1 Diabetes
Diabetes care, 2011Co-Authors: Sunil Zachariah, A. Margot Umpleby, F. Shojaee-moradie, Ben Sheldon, Nicola Jackson, K. Backhouse, Sigurd Johnsen, Richard H. Jones, David Russell-jonesAbstract:OBJECTIVE Insulin Detemir lacks the usual propensity for Insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure. RESEARCH DESIGN AND METHODS A 32-week, randomized crossover design trial was undertaken in 23 patients with type 1 diabetes. Patients on a basal-bolus regimen (with Insulin aspart as the bolus Insulin) were randomly assigned to Insulin Detemir or NPH Insulin as a basal Insulin for 16 weeks, followed by the other basal Insulin for 16 weeks. At the end of each 16-week period, total energy expenditure, resting energy expenditure, diet-induced thermogenesis, activity energy expenditure, energy intake, weight change, glycemic control, hypoglycemic episodes, and hormones that affect satiety and fuel partitioning were measured. RESULTS After 16 weeks, weight change was −0.69 ± 1.85 kg with Insulin Detemir and +1.7 ± 2.46 kg with NPH Insulin ( P P = 0.026). There was no significant difference in any measure of energy expenditure, HbA 1c percentage, or number of hypoglycemic episodes. Leptin was lower and resistin was higher with Insulin Detemir compared with NPH Insulin ( P = 0.039, P = 0.047). After the meal, ghrelin and pancreatic polypeptide levels ( P = 0.002, P = 0.001) were higher with Insulin Detemir. CONCLUSIONS The reduced weight gain with Insulin Detemir compared with NPH Insulin is attributed to reduced energy intake rather than increased energy expenditure. This may be mediated by a direct or indirect effect of Insulin Detemir on the hormones that control satiety.
-
Insulin Detemir and basal Insulin therapy.
Endocrinology and Metabolism Clinics of North America, 2007Co-Authors: David Russell-jonesAbstract:With the introduction of Insulin Detemir (Levemir® [Novo Nordisk A/S, Bagsvaerd, Denmark]), a long-acting basal Insulin analog, it is an opportune moment to reevaluate the use of basal Insulin therapy and consider current treatment strategies, including the use of Insulin Detemir. This review examines the need for effective treatment options for diabetes and the economic burden of this disease. The importance of achieving glycemic control targets and the role of basal Insulin therapy are discussed. Finally, the use of Insulin Detemir is briefly reviewed with a look at its clinical pharmacology, its use in basal Insulin therapy, and its cost-effectiveness.
-
Insulin Detemir Offers Improved Glycemic Control Compared With NPH Insulin in People With Type 1 Diabetes: A randomized clinical trial.
Diabetes care, 2004Co-Authors: Philip Home, David Russell-jones, Paul Anthony Bartley, Helene Hanaire-broutin, Jan-evert Heeg, Pascale Abrams, Mona Landin-olsson, Birgitte Hylleberg, Hanne Lang, Eberhard DraegerAbstract:OBJECTIVE —Insulin Detemir is a soluble long-acting basal Insulin analog designed to overcome the limitations of conventional basal Insulin formulations. Accordingly, Insulin Detemir has been compared with NPH Insulin with respect to glycemic control (HbA 1c , prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration. RESEARCH DESIGN AND METHODS —People with type 1 diabetes ( n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either Insulin Detemir or NPH Insulin. Insulin Detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDet morn+bed ) or at a 12-h interval (IDet 12h ). NPH Insulin was administered before breakfast and at bedtime. Mealtime Insulin was given as the rapid-acting Insulin analog Insulin aspart. RESULTS —With both Insulin Detemir groups, clinic fasting plasma glucose was lower than with NPH Insulin (IDet 12h vs. NPH, −1.5 mmol/l [95% CI −2.51 to −0.48], P = 0.004; IDet morn+bed vs. NPH, −2.3 mmol/l (−3.32 to −1.29), P P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both Insulin Detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH Insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDet morn+bed group ( P 1c for each Insulin Detemir group was not different from the NPH group, HbA 1c for the pooled Insulin Detemir groups was significantly lower than for the NPH group (mean difference −0.18% [−0.34 to −0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both Detemir groups (both P 12h vs. NPH, −0.8 kg [−1.44 to −0.24], P = 0.006; IDet morn+bed vs. NPH, −0.6 kg [−1.23 to −0.03], P = 0.040). CONCLUSIONS —Overall glycemic control with Insulin Detemir was improved compared with NPH Insulin. The data provide a basis for tailoring the timing of administration of Insulin Detemir to the individual person’s needs.
Thomas R Pieber - One of the best experts on this subject based on the ideXlab platform.
-
Bioavailability of Insulin Detemir and human Insulin at the level of peripheral interstitial fluid in humans, assessed by open-flow microperfusion.
Diabetes obesity & metabolism, 2015Co-Authors: Manfred Bodenlenz, M. Ellmerer, Lukas Schaupp, L. V. Jacobsen, Johannes Plank, Gernot Brunner, Andrea Wutte, Birgit Aigner, Selma Mautner, Thomas R PieberAbstract:Aims To find an explanation for the lower potency of Insulin Detemir observed in humans compared with unmodified human Insulin by investigating Insulin Detemir and human Insulin concentrations directly at the level of peripheral Insulin-sensitive tissues in humans in vivo. Methods Euglycaemic-hyperInsulinaemic clamp experiments were performed in healthy volunteers. Human Insulin was administered i.v. at 6 pmol/kg/min and Insulin Detemir at 60 pmol/kg/min, achieving a comparable steady-state pharmacodynamic action. In addition, Insulin Detemir was doubled to 120 pmol/kg/min. Minimally invasive open-flow microperfusion (OFM) sampling methodology was combined with inulin calibration to quantify human Insulin and Insulin Detemir in the interstitial fluid (ISF) of subcutaneous adipose and skeletal muscle tissue. Results The human Insulin concentration in the ISF was ∼115 pmol/l or ∼30% of the serum concentration, whereas the Insulin Detemir concentration in the ISF was ∼680 pmol/l or ∼2% of the serum concentration. The molar Insulin Detemir interstitial concentration was five to six times higher than the human Insulin interstitial concentration and metabolic clearance of Insulin Detemir from serum was substantially reduced compared with human Insulin. Conclusions OFM proved useful for target tissue measurements of human Insulin and the analogue Insulin Detemir. Our tissue data confirm a highly effective retention of Insulin Detemir in the vascular compartment. The higher Insulin Detemir relative to human Insulin tissue concentrations at comparable pharmacodynamics, however, indicate that the lower potency of Insulin Detemir in humans is attributable to a reduced effect in peripheral Insulin-sensitive tissues and is consistent with the reduced in vitro receptor affinity.
-
Open flow microperfusion: pharmacokinetics of human Insulin and Insulin Detemir in the interstitial fluid of subcutaneous adipose tissue
Diabetes obesity & metabolism, 2014Co-Authors: Christian Höfferer, Erica Nishimura, Christian L. Brand, Selma Mautner, D. Tutkur, Christian Fledelius, Thomas J. Alsted, J. Damgaard, C.b. Jeppesen, Thomas R PieberAbstract:Aims To compare the time profile of Insulin Detemir and human Insulin concentrations in the interstitial fluid (ISF) of subcutaneous adipose tissue during constant i.v. infusion and to investigate the relationship between the pharmacokinetics of both Insulin molecules in plasma and the ISF of subcutaneous adipose tissue. Methods During a 6-h hyperInsulinaemic–euglycaemic clamp (plasma glucose level 8 mmol/l) human Insulin (21 and 42 pmol/min/kg) or Insulin Detemir (209 and 417 pmol/min/kg) were infused i.v. in eight rats per dose level. Open flow microperfusion (OFM) was used to continuously assess interstitial Insulin concentrations in subcutaneous adipose tissue. Results At the lower infusion rate, Insulin Detemir appeared significantly later in the ISF than in the plasma (p
-
Proportional dose-response relationship and lower within-patient variability of Insulin Detemir and NPH Insulin in subjects with type 1 diabetes mellitus.
Experimental and clinical endocrinology & diabetes : official journal German Society of Endocrinology [and] German Diabetes Association, 2007Co-Authors: Andrea Wutte, Johannes Plank, M Bodenlenz, C Magnes, Werner Regittnig, Frank Sinner, Milan Zdravkovic, Rønn B, Thomas R PieberAbstract:AIMS: This study was conducted to evaluate the dose ratio of Insulin Detemir and neutral protamine Hagedorn (NPH) Insulin over a range of therapeutically relevant subcutaneous doses. METHODS: The study was a randomized, double-blind, crossover 24-h-iso-glycemic clamp trial in 12 C-peptide-negative type 1 diabetic patients. Each subject received, by an incomplete block design selection, two of three possible doses of Insulin Detemir (0.15, 0.3, 0.6 U/kg) and NPH Insulin (0.15, 0.3, 0.6 IU/kg), respectively. A detailed assessment of endogenous glucose production (EGP) and glucose uptake was performed, by use of stable isotopic labeled glucose tracer (D-[6,6- 2 H 2 ] glucose). RESULTS: Dose proportionality was observed within the tested dose range. Regarding unit dose ratio, 0.68 U Insulin Detemir equals 1 IU NPH Insulin (95% CI [0.35; 1.30]). There was no statistically significant difference in effect on the area under the curve (AUC) of glucose infusion rate (GIR) (AUC GIR ) and the maximal GIR (GIR max ) values, when comparing U (Insulin Detemir) to IU (NPH Insulin). The pharmacodynamic within-subject profile was lower with Insulin Detemir in regard to AUC GIR 0-24 h , GIR max and duration of action ( P
-
proportional dose response relationship and lower within patient variability of Insulin Detemir and nph Insulin in subjects with type 1 diabetes mellitus
Experimental and Clinical Endocrinology & Diabetes, 2007Co-Authors: Andrea Wutte, Johannes Plank, M Bodenlenz, C Magnes, Werner Regittnig, Frank Sinner, B Ronn, Milan Zdravkovic, Thomas R PieberAbstract:AIMS: This study was conducted to evaluate the dose ratio of Insulin Detemir and neutral protamine Hagedorn (NPH) Insulin over a range of therapeutically relevant subcutaneous doses. METHODS: The study was a randomized, double-blind, crossover 24-h-iso-glycemic clamp trial in 12 C-peptide-negative type 1 diabetic patients. Each subject received, by an incomplete block design selection, two of three possible doses of Insulin Detemir (0.15, 0.3, 0.6 U/kg) and NPH Insulin (0.15, 0.3, 0.6 IU/kg), respectively. A detailed assessment of endogenous glucose production (EGP) and glucose uptake was performed, by use of stable isotopic labeled glucose tracer (D-[6,6- 2 H 2 ] glucose). RESULTS: Dose proportionality was observed within the tested dose range. Regarding unit dose ratio, 0.68 U Insulin Detemir equals 1 IU NPH Insulin (95% CI [0.35; 1.30]). There was no statistically significant difference in effect on the area under the curve (AUC) of glucose infusion rate (GIR) (AUC GIR ) and the maximal GIR (GIR max ) values, when comparing U (Insulin Detemir) to IU (NPH Insulin). The pharmacodynamic within-subject profile was lower with Insulin Detemir in regard to AUC GIR 0-24 h , GIR max and duration of action ( P<0.05). There was a tendency for a greater reduction of EGP with Insulin Detemir than with NPH Insulin in regard to the area over the curve (AOC) of EGP in 24 hours (AOC EGP 0-24 h ) ( P=0.07) and minimal EPG (EGP min ) ( P=0.02). CONCLUSIONS: These data show that Insulin Detemir is dose-proportional to NPH Insulin in type 1 diabetic patients at clinically relevant doses. The data indicate that Insulin Detemir has a lower degree of within-subject variability.
-
comparison of Insulin Detemir and Insulin glargine in subjects with type 1 diabetes using intensive Insulin therapy
Diabetic Medicine, 2007Co-Authors: Thomas R Pieber, L Mordhorst, M A Gall, H C Treichel, B Hompesch, Areti Philotheou, L I RobertsonAbstract:Aims To compare glycaemic control and risk of hypoglycaemia of twice-daily Insulin Detemir with once-daily Insulin glargine in subjects with Type 1 diabetes. Methods In this 26-week, multicentre, open-label, parallel-group trial, 320 subjects with Type 1 diabetes received either Insulin Detemir twice daily or Insulin glargine once daily. each in combination with premeal Insulin aspart. Results After 26 weeks, HbA1c had decreased from 8.8 to 8.2% in the Insulin Detemir group and from 8.7 to 8.2% in the Insulin glargine group. Home-measured fasting plasma glucose (PG) was lower with Insulin glargine than with Insulin Detemir (7.0 vs. 7.7 mmol/l, P < 0.001). The overall shape of the home-measured nine-point PG profiles was comparable between treatments (P = 0.125). Overall, there was no significant difference in within-subject variation in PG (P = 0.437). Within-subject variation in predinner PG was lower with Insulin Detemir than with Insulin glargine (P < 0.05). The overall risk of hypoglycaemia was similar with no differences in confirmed hypoglycaemia. However, the risk of severe and nocturnal hypoglycaemia was 72% and 32%, respectively, lower with Insulin Detemir than with Insulin glargine (P < 0.05). Body weight gain was not significantly different comparing Insulin Detemir and Insulin glargine (0.52 kg vs. 0.96 kg, P = 0.193). Conclusions Treatment with twice-daily Insulin Detemir or once-daily Insulin glargine, each in combination with Insulin aspart, resulted in similar glycaemic control. The overall risk of hypoglycaemia was comparable, whereas the risks of both severe and nocturnal hypoglycaemia were significantly lower with Insulin Detemir.
H.-u. Häring - One of the best experts on this subject based on the ideXlab platform.
-
Weight-sparing effect of Insulin Detemir: a consequence of central nervous system-mediated reduced energy intake?
Diabetes obesity & metabolism, 2015Co-Authors: David Russell-jones, Kjeld Hermansen, Thomas Danne, Kevin D. Niswender, K. Robertson, N. Thalange, J. R. Vasselli, B. Yildiz, H.-u. HäringAbstract:Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and Insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that Insulin Detemir, a basal Insulin analogue, exerts a unique weight‐sparing effect compared with other basal Insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to Insulin Detemir and comparator basal Insulins. The following models have been proposed: Insulin Detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that Insulin Detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter‐regulatory response to Insulin through restoration of the hepatic–peripheral Insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight‐sparing effect of Insulin Detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.
-
Tissue selectivity of Insulin Detemir action in vivo
Diabetologia, 2006Co-Authors: A. M. Hennige, T. Sartorius, O. Tschritter, H. Preissl, A. Fritsche, P. Ruth, H.-u. HäringAbstract:Aims/hypothesis Recombinant DNA technology is a useful tool that can be used to create Insulin analogues with modified absorption kinetics to improve glycaemic control in patients with type 1 and type 2 diabetes. Among conventional Insulin analogues, which are usually created by amino acid exchange, Insulin Detemir is the first analogue to be acylated with a fatty acid to enable reversible albumin binding. In this study we determined activation of the Insulin receptor (IR)-signalling cascade by Insulin Detemir at the level of IR and IR substrate (Irs) phosphorylation, as well as downstream signalling elements such as phosphatidylinositol 3-kinase and Akt, and performed epidural EEG in vivo. Methods C57Bl/6 mice were injected i.v. with either Insulin Detemir or human Insulin and Western blot analysis was performed on liver, muscle, hypothalamic and cerebrocortical tissues. Moreover, cerebrocortical activity was detected by EEG in awake mice and cerebral Insulin concentrations were measured following human Insulin and Insulin Detemir injection. Results The time course and extent of IR phosphorylation in peripheral tissues were similar following Insulin Detemir treatment compared with human Insulin, but Insulin signalling in hypothalamic and cerebrocortical tissue determined by tyrosine-phosphorylation of the IR and Irs2 proteins occurred faster and was enhanced due to a higher Insulin Detemir concentration in the brain. Moreover, epidural EEG in mice displayed increased cortical activity using Insulin Detemir. Conclusions/interpretation Taken together, these data suggest that Insulin Detemir has a tissue-selective action, with a relative preference for brain compared with peripheral tissues.
-
Tissue selectivity of Insulin Detemir action in vivo.
Diabetologia, 2006Co-Authors: Anita M Hennige, P. Ruth, Tina Sartorius, Andreas Fritsche, Otto Tschritter, Hubert Preissl, H.-u. HäringAbstract:Aims/hypothesis Recombinant DNA technology is a useful tool that can be used to create Insulin analogues with modified absorption kinetics to improve glycaemic control in patients with type 1 and type 2 diabetes. Among conventional Insulin analogues, which are usually created by amino acid exchange, Insulin Detemir is the first analogue to be acylated with a fatty acid to enable reversible albumin binding. In this study we determined activation of the Insulin receptor (IR)-signalling cascade by Insulin Detemir at the level of IR and IR substrate (Irs) phosphorylation, as well as downstream signalling elements such as phosphatidylinositol 3-kinase and Akt, and performed epidural EEG in vivo.
Melanie J. Davies - One of the best experts on this subject based on the ideXlab platform.
-
Reduced weight gain with Insulin Detemir compared to NPH Insulin is not explained by a reduction in hypoglycemia.
Diabetes technology & therapeutics, 2008Co-Authors: Melanie J. Davies, Tadeusz Derezinski, Claus Bang Pedersen, Per ClausonAbstract:Abstract Background: Weight gain often occurs when Insulin therapy is initiated. The long-acting Insulin analog Insulin Detemir has been shown to be effective and well tolerated when used in basal-bolus regimens or as an add-on to oral antidiabetic drugs (OADs) and causes less weight gain than other Insulins. The aim of this exploratory analysis was to investigate any correlations between weight change and occurrence of hypoglycemia with NPH Insulin and Insulin Detemir. Methods: The analysis was based on a 26-week, randomized, multicenter, open-label, parallel-group trial in which glycemic control, hypoglycemia, and weight change were compared between Insulin Detemir and NPH Insulin. A total of 476 Insulin-naive patients with type 2 diabetes treated with one or two OADs added Insulin Detemir (n = 237) or NPH Insulin (n = 239) morning and evening to their current oral treatment. Weight gain data from this study were analyzed as a function of hypoglycemia frequency. Results: Both groups achieved excellent g...
-
Does Insulin Detemir have a role in reducing risk of Insulin associated weight gain
Diabetes obesity & metabolism, 2007Co-Authors: Kjeld Hermansen, Melanie J. DaviesAbstract:Weight gain is often perceived as inevitable with Insulin therapy, particularly as we strive for tight glycaemic control and are using increasingly proactive Insulin titration regimes. The United Kingdom Prospective Diabetes Study documented that weight gain occurs most rapidly soon after Insulin therapy is first initiated. The timing of this side effect is particularly undesirable, as weight gain may interfere with patients' adjustment to Insulin therapy and may undermine appropriate diabetes self-management behaviours. Until recently, many patients had little alternative other than to accept unwanted weight gain if they were to achieve sufficient glycaemic control to reduce risk of chronic complications of diabetes. Insulin Detemir is a novel basal Insulin analogue that has consistently been shown in randomized, controlled trials to have a weight-sparing effect (i.e. weight loss or reduced weight gain compared with other Insulins) in both type 1 and type 2 diabetes. Indeed, unlike neutral protamine Hagedorn (NPH) Insulin, the weight-sparing effect of Insulin Detemir appears to be most prominent in people who are the most obese. The mechanisms behind the weight-sparing effect of Insulin Detemir are still being clarified. Reduced risk of hypoglycaemia with Insulin Detemir, coupled with a more consistent and reliable delivery of the desired dose than is available with traditional basal Insulin, such as NPH, has been proposed to minimize defensive snacking by patients, and help to limit weight gain. However, even if this was proven, it would be unlikely to fully explain the weight-sparing effect of Insulin Detemir. Two additional theories have been put forward. One suggests that due to its novel method of prolonging action via acylation and albumin binding, Insulin Detemir may differentially influence hepatocytes more than peripheral tissues, thus effectively suppressing hepatic glucose output without promoting lipogenesis in the periphery. The second theory suggests that Insulin Detemir may be more effective than human Insulin in communicating satiety signals within the central nervous system. Further clarification of these hypotheses is required.
S G H A Swinnen - One of the best experts on this subject based on the ideXlab platform.
-
Insulin Detemir versus Insulin glargine for type 2 diabetes mellitus
Cochrane Database of Systematic Reviews, 2011Co-Authors: S G H A Swinnen, A C R Simon, Frits Holleman, Joost B L Hoekstra, Hans J DevriesAbstract:Background Chronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require Insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal Insulin treatment regimens for type 2 diabetes, but the long-acting Insulin analogues seem beneficial. Several reviews have compared either Insulin Detemir or Insulin glargine to NPH Insulin, but research directly comparing both Insulin analogues is limited. Objectives To assess the effects of Insulin Detemir and Insulin glargine compared with each other in the treatment of type 2 diabetes mellitus. Search methods We searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011. Selection criteria All randomised controlled trials comparing Insulin Detemir with Insulin glargine with a duration of 12 weeks or longer were included. Data collection and analysis Two authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed. Main results This review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either Insulin Detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin Detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting Insulin Detemir twice-daily at the end of trial. Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups. The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups. Insulin Detemir was associated with less weight gain. Treatment with Insulin glargine resulted in a lower daily basal Insulin dose and a lower number of injection site reactions. There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups. Authors' conclusions Our analyses suggest that there is no clinically relevant difference in efficacy or safety between Insulin Detemir and Insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control Insulin Detemir was often injected twice-daily in a higher dose but with less weight gain, while Insulin glargine was injected once-daily, with somewhat fewer injection site reactions.
-
The Cochrane Library - Insulin Detemir versus Insulin glargine for type 2 diabetes mellitus.
The Cochrane database of systematic reviews, 2011Co-Authors: S G H A Swinnen, A C R Simon, Frits Holleman, Joost B L Hoekstra, J. Hans DevriesAbstract:Background Chronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require Insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal Insulin treatment regimens for type 2 diabetes, but the long-acting Insulin analogues seem beneficial. Several reviews have compared either Insulin Detemir or Insulin glargine to NPH Insulin, but research directly comparing both Insulin analogues is limited. Objectives To assess the effects of Insulin Detemir and Insulin glargine compared with each other in the treatment of type 2 diabetes mellitus. Search methods We searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011. Selection criteria All randomised controlled trials comparing Insulin Detemir with Insulin glargine with a duration of 12 weeks or longer were included. Data collection and analysis Two authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed. Main results This review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either Insulin Detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin Detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting Insulin Detemir twice-daily at the end of trial. Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups. The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups. Insulin Detemir was associated with less weight gain. Treatment with Insulin glargine resulted in a lower daily basal Insulin dose and a lower number of injection site reactions. There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups. Authors' conclusions Our analyses suggest that there is no clinically relevant difference in efficacy or safety between Insulin Detemir and Insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control Insulin Detemir was often injected twice-daily in a higher dose but with less weight gain, while Insulin glargine was injected once-daily, with somewhat fewer injection site reactions.
-
higher dose requirements with Insulin Detemir in type 2 diabetes three cases and a review of the literature
Diabetes Research and Clinical Practice, 2009Co-Authors: S G H A Swinnen, Hans J DevriesAbstract:We report on three type 2 diabetic patients whose daily basal Insulin dose requirements were substantially reduced after switching from Insulin Detemir to Insulin glargine. Meta-analysis of three randomised trials of basal Insulin initiation confirmed this increased Insulin Detemir dose requirement in type 2 patients. Potential explanations are discussed.