ADO09, a co-formulation of pramlintide and insulin A21G, lowers body weight versus insulin lispro in type 1 diabetes.

AIM: To study safety, efficacy and weight loss with ADO09, a co-formulation of insulin A21G and pramlintide, in type 1 diabetes. MATERIALS AND METHODS: A randomized, two-arm ambulatory 16-week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment. RESULTS: A significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed. CONCLUSIONS: These results extend previous observations on the efficacy and safety of this insulin/pramlintide co-formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia.

Tirzepatide vs Insulin Lispro Added to Basal Insulin in Type 2 Diabetes: The SURPASS-6 Randomized Clinical Trial.

Importance: Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. Efficacy and safety of adding tirzepatide vs prandial insulin to treatment in patients with inadequate glycemic control with basal insulin have not been described. Objective: To assess the efficacy and safety of tirzepatide vs insulin lispro as an adjunctive therapy to insulin glargine. Design, Setting, and Participants: This open-label, phase 3b clinical trial was conducted at 135 sites in 15 countries (participants enrolled from October 19, 2020, to November 1, 2022) in 1428 adults with type 2 diabetes taking basal insulin. Interventions: Participants were randomized (in a 1:1:1:3 ratio) to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [n = 236]) or prandial thrice-daily insulin lispro (n = 708). Main Outcomes and Measures: Outcomes included noninferiority of tirzepatide (pooled cohort) vs insulin lispro, both in addition to insulin glargine, in HbA1c change from baseline at week 52 (noninferiority margin, 0.3%). Key secondary end points included change in body weight and percentage of participants achieving hemoglobin A1c (HbA1c) target of less than 7.0%. Results: Among 1428 randomized participants (824 [57.7%] women; mean [SD] age, 58.8 [9.7] years; mean [SD] HbA1c, 8.8% [1.0%]), 1304 (91.3%) completed the trial. At week 52, estimated mean change from baseline in HbA1c with tirzepatide (pooled cohort) was -2.1% vs -1.1% with insulin lispro, resulting in mean HbA1c levels of 6.7% vs 7.7% (estimated treatment difference, -0.98% [95% CI, -1.17% to -0.79%]; P < .001); results met noninferiority criteria and statistical superiority was achieved. Estimated mean change from baseline in body weight was -9.0 kg with tirzepatide and 3.2 kg with insulin lispro (estimated treatment difference, -12.2 kg [95% CI, -13.4 to -10.9]). The percentage of participants reaching HbA1c less than 7.0% was 68% (483 of 716) with tirzepatide and 36% (256 of 708) with insulin lispro (odds ratio, 4.2 [95% CI, 3.2-5.5]). The most common adverse events with tirzepatide were mild to moderate gastrointestinal symptoms (nausea: 14%-26%; diarrhea: 11%-15%; vomiting: 5%-13%). Hypoglycemia event rates (blood glucose level <54 mg/dL or severe hypoglycemia) were 0.4 events per patient-year with tirzepatide (pooled) and 4.4 events per patient-year with insulin lispro. Conclusions and Relevance: In people with inadequately controlled type 2 diabetes treated with basal insulin, weekly tirzepatide compared with prandial insulin as an additional treatment with insulin glargine demonstrated reductions in HbA1c and body weight with less hypoglycemia. Trial Registration: ClinicalTrials.gov Identifier: NCT04537923.

Ultra-Fast Insulin-Pramlintide Co-Formulation for Improved Glucose Management in Diabetic Rats.

Dual-hormone replacement therapy with insulin and amylin in patients with type 1 diabetes has the potential to improve glucose management. Unfortunately, currently available formulations require burdensome separate injections at mealtimes and have disparate pharmacokinetics that do not mimic endogenous co-secretion. Here, amphiphilic acrylamide copolymers are used to create a stable co-formulation of monomeric insulin and amylin analogues (lispro and pramlintide) with synchronous pharmacokinetics and ultra-rapid action. The co-formulation is stable for over 16 h under stressed aging conditions, whereas commercial insulin lispro (Humalog) aggregates in 8 h. The faster pharmacokinetics of monomeric insulin in this co-formulation result in increased insulin-pramlintide overlap of 75 ± 6% compared to only 47 ± 7% for separate injections. The co-formulation results in similar delay in gastric emptying compared to pramlintide delivered separately. In a glucose challenge, in rats, the co-formulation reduces deviation from baseline glucose compared to insulin only, or separate insulin and pramlintide administrations. Further, comparison of interspecies pharmacokinetics of monomeric pramlintide suggests that pharmacokinetics observed for the co-formulation will be well preserved in future translation to humans. Together these results suggest that the co-formulation has the potential to improve mealtime glucose management and reduce patient burden in the treatment of diabetes.

Weight loss in patients with type 2 diabetes receiving once-weekly dulaglutide plus insulin lispro or insulin glargine plus insulin lispro: A post-hoc analysis of the AWARD-4 study across baseline body mass index subgroups.

AIMS: Insulin-treated patients with type 2 diabetes (T2D) and obesity are challenged in achieving body weight stability or reduction, in addition to glycaemic control. Post-hoc analyses of body weight and insulin dose data from the AWARD-4 trial involved comparison of treatment with once-weekly dulaglutide 1.5 mg (N = 295) or 0.75 mg (N = 293) and treatment with daily insulin glargine (N = 296), each with prandial insulin lispro (± metformin). MATERIALS AND METHODS: Changes in weight and in the proportion of patients without weight gain or with weight loss of at least 3%, 5% or 10% or composites of HbA1c less than 7% without weight gain and weight loss of at least 3% after 52 weeks were compared between the dulaglutide (either dose) groups and the insulin glargine group, overall and by baseline BMI (<30, 30-<35, ≥35 kg/m2 ), using analysis of covariance and logistic regression, including interaction terms. RESULTS: The following parameters were statistically significant (P < 0.01) in favour of the dulaglutide-treated groups, at lower mean total daily insulin doses, vs the insulin glargine group. The achieved targets were more pronounced with dulaglutide 1.5 mg than with insulin glargine: LSM weight change difference, -3.23 kg; proportion of patients without weight gain, 49.0% vs 19.0%; proportion of patients with weight loss ≥3%, 21.7% vs 5.7% or with weight loss ≥5%, 10.5% vs 2.4%; proportion of patients with HbA1c <7% without weight gain, 26.2% vs 7.9%; proportion of patients with HbA1c <7% and weight loss ≥3%, 11.9% vs 1.4%, respectively. Treatment effect for these parameters was not significantly different across BMI categories. CONCLUSIONS: Larger proportions of patients in late-stage T2D needing treatment intensification achieved glycemic control without weight gain or with weight loss at lower insulin doses with once-weekly dulaglutide plus daily prandial insulin than with a basal-bolus insulin regimen, overall and across all three BMI subgroups.

Effectiveness of insulin analogs compared with human insulins in pregnant women with diabetes mellitus: systematic review and meta-analysis / Efetividade dos análogos da insulina comparados às insulinas humanas em gestantes com diabetes mellitus: Revisão sistemática com metanálise

Abstract Diabetes during pregnancy has been linked to unfavorable maternal-fetal outcomes. Human insulins are the first drug of choice because of the proven safety in their use. However, there are still questions about the use of insulin analogs during pregnancy. The objective of the present study was to determine the effectiveness of insulin analogs compared withhuman insulin in the treatment of pregnant women with diabetes througha systematic review withmeta-analysis. The search comprised the period since the inception of each database until July 2017, and the following databases were used:MEDLINE, CINAHL, EMBASE, ISIWeb of Science, LILACS, Scopus, SIGLE andGoogle Scholar.We have selected 29 original articles: 11 were randomized clinical trials and 18 were observational studies.We have explored data from 6,382 participants. All of the articles were classified as having an intermediate to high risk of bias. The variable that showed favorable results for the use of insulin analogs was gestational age, with a mean difference of - 0.26 (95 % confidence interval [CI]: 0.03-0.49; p = 0.02), but with significant heterogeneity (Higgins test [I2] = 38%; chi-squared test [χ2] = 16.24; degree of freedom [DF] = 10; p = 0.09). This result, in the clinical practice, does not compromise the fetal well-being, since all babies were born at term. There was publication bias in the gestational age and neonatal weight variables. To date, the evidence analyzed has a moderate-to-high risk of bias and does not allow the conclusion that insulin analogs are more effective when compared with human insulin to treat diabetic pregnant women.

Resumo Diabetes durante a gestação tem sido relacionado a desfechos materno-fetais desfavoráveis. As insulinas humanas são a primeira escolha medicamentosa, devido à comprovada segurança no seu uso. Entretanto, ainda há questionamentos sobre o uso dos análogos da insulina na gestação. O objetivo do presente estudo foi determinar a efetividade dos análogos da insulina comparados às insulinas humanas no tratamento de gestantes com diabetes por meio de uma revisão sistemática com metanálise. A busca compreendeu desde o início de cada base de dados até julho de 2017, e foi realizada nos seguintes bancos de dados: MEDLINE, CINAHL, EMBASE, ISI Web of Science, LILACS, Scopus, SIGLE e Google Scholar. Selecionamos 29 artigos originais, sendo 11 ensaios clínicos randomizados e 18 estudos observacionais. Exploramos dados de 6.382 participantes. Todos os artigos foram classificados como sendo de intermediário a alto risco de viés. A variável que demonstrou resultado favorável ao uso dos análogos da insulina foi idade gestacional, com uma diferençamédia de - 0.26 (95% índice de confiança [IC]: 0.03-0.49; p = 0.02), porém com heterogeneidade significativa (teste de Higgins [I2] = 38%; teste do qui quadrado [χ2] =16.24; graus de liberdade [GL] =10; p = 0.09). Esse resultado, na prática clínica, não compromete o bem-estar fetal, uma vez que todos os bebês nasceram a termo. Houve viés de publicação nas variáveis idade gestacional e peso neonatal. Até o momento, as evidências analisadas possuem um risco de viés moderado a elevado e não permitem concluir que os análogos da insulina sejam mais efetivos em comparação às insulinas humanas para tratar gestantes diabéticas.

Use of lispro insulin for treatment of diabetic ketoacidosis in cats.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of lispro insulin for the treatment of feline diabetic ketoacidosis (DKA). Times to resolution of hyperglycaemia, ketosis and acidosis were compared between cats treated with continuous rate infusion (CRI) of lispro insulin and cats treated with CRI of regular insulin. METHODS: Client-owned cats with naturally occurring DKA, newly diagnosed with diabetes mellitus (DM) or already receiving treatment for DM, were included. Diagnosis of DKA involved the presence of at least two clinical signs consistent with DKA (eg, polyuria/polydipsia, anorexia, severe lethargy, vomiting and dehydration), blood glucose (BG) concentration >13.9 mmol/l (>250 mg/dl), blood beta hydroxybutyrate (BHB) concentration >2.5 mmol/l and venous pH <7.3 or bicarbonate <15 mEq/l. Cats were treated with a standard protocol of an intravenous (IV) CRI of regular insulin (group R) or lispro insulin (group L). The time to resolution of DKA was defined as the time interval from when the IV CRI of insulin began until marked hyperglycaemia (BG >13.9 mmol/l [>250 mg/dl]), ketosis (BHB concentration >1 mmol/l) and acidosis (venous pH <7.3 and/or bicarbonate <15 mEq/l) resolved. RESULTS: Eighteen DKA cases (nine per group) were enrolled into the study. There were no significant differences in the median time to resolution of three variables (hyperglycaemia, ketosis and acidosis) between the two groups. Two cats in group R developed hypoglycaemia during the CRI of insulin. One cat in group L and three cats in group R developed hypophosphataemia, which required phosphate supplementation. CONCLUSIONS AND RELEVANCE: IV CRI of lispro insulin has few side effects and appears to be as effective as IV CRI of regular insulin in the treatment of cats with DKA.

[Hypoglycemia due to antibodies to exogenous insulin in a patient with type 2 diabetes ­ a case report of treatment with new generation oral hypoglycemic agents].

Hypoglycemic syndromes associated with immune reactions against insulin are rare phenomena described predominantly in Asians. Steroid therapy, immunosuppression or plasmapheresis is often required. Case report: A 73-year-old White woman with a 20-year history of type 2 diabetes was admitted to hospital due to recurrent incidents of hypoglycemia that started several months after insulin initiation (lispro 75/25) and increased in severity over the next 5 years. They were accompanied by postprandial hyperglycemia up to 25 mmol/l. The patient's glycated hemoglobin (HbA1c) was 70 mmol/ mol (8.6%). During hypoglycemic episodes recorded serum C-peptide was 0.57-0.73 nmol/l (1.7-2.2 ng/ml), while insulin concentration exceeded 7000 pmol/l (1000 mIU/l). Surreptitious insulin administration was ruled out as was, based on diagnostic imaging, the presence of an insulin secreting tumor. Anti-insulin antibody (AIA) level measured by 125I-insulin binding method was 92.5% (normal < 8.2%). Hypoglycemic episodes occurred for four days after discontinuation of insulin therapy and then resolved completely. Good glycemic control was maintained with metformin, acarbose and dapagliflozin. Three months later dapagliflozin was replaced with vildagliptine due to poor tolerance of a SGLT-2 inhibitor. Patient's HbA1c was 54 mmol/mol (7.1%), total fasting insulin level 2577 pmol/l and AIA binding 85.9%. Over the next year the patient has not experienced hypoglycemia and maintained good glycemic control, as HbA1c level was 53 mmol/l (7.0%) and AIA binding 39.5%. Conclusions: In this rare case of a patient with diabetes and hypoglycemic syndrome related to AIA, we achieved a rapid and stable remission of hypoglycemia without immunosuppression. Good glycemic control, despite 20-year history of diabetes was achieved with oral hypoglycemic agents.

The effects of exenatide twice daily compared to insulin lispro added to basal insulin in Latin American patients with type 2 diabetes: A retrospective analysis of the 4B trial.

AIMS: Socioeconomic changes in Latin American countries have led to an increased prevalence of type 2 diabetes (T2D). We examined the effects of exenatide twice daily (BID) or insulin lispro, each added to insulin glargine, in Latin American patients with T2D. METHODS: This was a subgroup analysis of patients from Argentina and Mexico in the 4B study (N=114). Patients with glycated hemoglobin (HbA1c) of 7.0-10.0% (53-86mmol/mol) after 12weeks of intensive basal insulin optimization were randomized to exenatide BID or thrice-daily insulin lispro added to insulin glargine and metformin. RESULTS: After 30weeks, addition of exenatide BID or insulin lispro resulted in significant (P<0.0001) reductions in HbA1c (exenatide BID: -0.9% [-10mmol/mol]; insulin lispro: -1.2% [-13mmol/mol]). Weight was stable in the exenatide BID group (-0.1kg) and increased significantly (+3.4kg; P<0.0001) with insulin lispro. Major and minor hypoglycemia occurred less frequently (40 vs. 253 events) with exenatide BID compared with insulin lispro. Gastrointestinal adverse events of nausea, diarrhea, and vomiting occurred more frequently with exenatide BID than with insulin lispro. CONCLUSIONS: Both exenatide BID and prandial insulin lispro, each added to basal insulin glargine, were effective at reducing HbA1c in Latin American patients. Treatment with exenatide BID resulted in stable weight but more gastrointestinal adverse events. Treatment with insulin lispro resulted in weight gain and an increased risk of hypoglycemia. These findings support the addition of exenatide BID to insulin glargine as an option for Latin American patients unable to achieve glycemic control on basal insulin alone.

Relationship of body mass index with efficacy of exenatide twice daily added to insulin glargine in patients with type 2 diabetes.

This post hoc analysis assessed the evidence behind common reimbursement practices by evaluating the relationship of body mass index (BMI) ranges (<30, 30-35 and >35 kg/m(2) ) with treatment effects of exenatide twice daily among patients with type 2 diabetes. Patients received exenatide twice daily added to insulin glargine in two 30-week studies (exenatide twice daily vs insulin lispro, n = 627; exenatide twice daily vs placebo, n = 259). No association of baseline BMI with changes in efficacy variables was observed. Glycated haemoglobin (HbA1c) reductions were significant (p < 0.0001) and similar across BMI range groups in the lispro-comparator study and greater for exenatide versus placebo in the placebo-controlled study. Significant weight loss occurred with exenatide across BMI range groups (p < 0.0001), while weight increased with both comparators. Achievement of HbA1c <7.0% (<53 mmol/mol) without weight gain was greater for exenatide versus comparators. Systolic blood pressure decreased across BMI range groups with exenatide in the lispro-comparator study (p < 0.0001); changes in lipids were not clinically meaningful. Minor hypoglycaemia was less frequent for exenatide versus insulin lispro. These findings suggest that BMI alone should not limit clinical decision-making or patient access to medication.

Post-Gastric Bypass Hyperinsulinemic Hypoglycemia: Fructose is a Carbohydrate Which Can Be Safely Consumed.

CONTEXT: Postprandial hypoglycemia after gastric bypass surgery is a serious problem. Available treatments are often ineffective. OBJECTIVE: The objective was to test the hypotheses that injection of rapid-acting insulin before a high-carbohydrate meal or replacement of other carbohydrates with fructose in the meal would prevent hypoglycemia. DESIGN: This was a randomized, crossover trial comparing a high-carbohydrate meal with premeal saline injection (control), a high-carbohydrate meal with premeal insulin injection, and a high-fructose meal with total carbohydrate content similar to the control meal. SETTING: The setting was an academic medical center. PATIENTS: Ten patients with post-gastric bypass hyperinsulinemic hypoglycemia participated. INTERVENTIONS: Interventions included lispro insulin injected before test meals and replacement of other carbohydrates with fructose in test meals. MAIN OUTCOME MEASURE: The main outcome measure was plasma glucose < 60 mg/dL after test meals. RESULTS: After the control meal, mean peak glucose and insulin were 173 ± 47 mg/dL and 134 ± 55 mU/L, respectively; mean glucose nadir was 44 ± 15 mg/dL; and eight of 10 subjects demonstrated glucose < 60 mg/dL. Five subjects demonstrated a glucose nadir < 40 mg/dL. There were no significant differences in the corresponding values after premeal insulin treatment, except that the mean glucose nadir of 34 ± 10 mg/dL was lower (P < .05). After the fructose meal, mean peak postprandial glucose and insulin were 117 ± 20 mg/dL and 45 ± 31 mU/L, respectively (both P < .001 for comparison with control), mean glucose nadir was 67 ± 10 mg/dL (P < .001), and two of 10 subjects demonstrated glucose < 60 mg/dL (P < .05). CONCLUSIONS: People with post-gastric bypass hypoglycemia can consume a meal sweetened with fructose with little risk of hypoglycemia. Treatment with rapid-acting insulin before a carbohydrate-containing meal did not prevent hypoglycemia.

Risk of breast cancer by individual insulin use: an international multicenter study.

OBJECTIVE Several studies have been published in 2009 suggesting a possible association between insulin glargine and increased risk of malignancies, including breast cancer. The objective of this study was to assess the relation between the individual insulins (glargine, aspart, lispro, and human insulin) and development of breast cancer. RESEARCH DESIGN AND METHODS Seven hundred seventy-five incident cases of primary invasive or in situ carcinoma breast cancer occurring in women with diabetes from 92 centers in the U.K., Canada, and France were matched to a mean of 3.9 diabetic community control subjects (n = 3,050; recruited from 580 general practices) by country, age, recruitment date, and diabetes type and management. The main risk model was a multivariate conditional logistic regression model with case/control status as the dependent variable and individual insulin use, 8 years preceding the index date, as the independent variable, controlling for past use of any insulin, oral antidiabetes drugs, reproductive factors, lifestyle, education, hormone replacement therapy and history of contraceptive use, BMI, comorbidities, diabetes duration, and annual number of physician visits. Glargine was also compared with every other insulin by computing all ratios using the variance-covariance matrix of logistic model parameters. RESULTS Adjusted odds ratios of breast cancer for each type of insulin versus no use of that insulin were 1.04 (95% CI 0.76-1.44) for glargine, 1.23 (0.79-1.92) for lispro, 0.95 (0.64-1.40) for aspart, and 0.81 (0.55-1.20) for human insulin. Two-by-two comparisons found no difference between glargine and the different types of insulins. Insulin dosage or duration of use and tumor stage did not change the results. CONCLUSIONS This international study found no difference in the risk of developing breast cancer in patients with diabetes among the different types of insulin with short- to mid-term duration of use. Longer-term studies would be of interest.

Efficacy and safety of insulin lispro in geriatric patients with type 2 diabetes: a retrospective analysis of seven randomized controlled clinical trials.

BACKGROUND AND AIMS: Glycemic control in geriatric patients with type 2 diabetes (T2DM) remains clinically challenging. The objective of this study was to compare the safety and efficacy of insulin lispro in patients C65 years (geriatric) to those\65 years (non-geriatric), using a metaanalysis of randomized controlled clinical trials (RCT). METHODS: This is a retrospective analysis of predefined endpoints from an integrated database of seven RCTs of T2DM patients treated with insulin lispro. The primary efficacy measure tested the non-inferiority of insulin lispro (geriatric vs. non-geriatric; non-inferiority margin 0.4 %) in terms of hemoglobin A1c (HbA1c) change from baseline to Month 3 (N = 1,525), with change from baseline to Month 6 as a supportive analysis (N = 885). Changes in HbA1c from baseline were evaluated with an analysis of covariance model. Secondary measures included incidence and rate of hypoglycemia, and incidence of cardiovascular events. RESULTS: Mean change in HbA1c from baseline to Month 3 was similar for geriatric (-0.97 %) and non-geriatric patients (-1.05 %); least-square (LS) mean difference (95 % CI) was 0.02 % (-0.11, 0.15 %; p = 0.756). Similar results were observed in patients treated up to Month 6; LS mean difference (95 % CI) was 0.07 % (-0.12, 0.26 %; p = 0.490). Decrease in HbA1c from baseline to Months 3 and 6 was non-inferior in geriatric compared with non-geriatric patients. There were no significant differences in the incidence and the rate of hypoglycemia, incidence of cardiovascular events, or other serious adverse events including malignancy, post-baseline between the two cohorts. CONCLUSION: Key measures of efficacy and safety in geriatric patients with T2DM were not significantly different from non-geriatric patients when utilizing insulin lispro. Insulin lispro may be considered a safe and efficacious therapeutic option for the management of T2DM in geriatric patients.

Safety and efficacy of sitagliptin therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes: a pilot, randomized, controlled study.

OBJECTIVE: This study investigated the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients. RESEARCH DESIGN AND METHODS: In this pilot, multicenter, open-label, randomized study, patients (n = 90) with a known history of T2D treated with diet, oral antidiabetic agents, or low total daily dose of insulin (≤0.4 units/kg/day) were randomized to receive sitagliptin alone or in combination with glargine insulin (glargine) or to a basal bolus insulin regimen (glargine and lispro) plus supplemental (correction) doses of lispro. Major study outcomes included differences in daily blood glucose (BG), frequency of treatment failures (defined as three or more consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL), and hypoglycemia between groups. RESULTS: Glycemic control improved similarly in all treatment groups. There were no differences in the mean daily BG after the 1st day of treatment (P = 0.23), number of readings within a BG target of 70 and 140 mg/dL (P = 0.53), number of BG readings >200 mg/dL (P = 0.23), and number of treatment failures (P > 0.99). The total daily insulin dose and number of insulin injections were significantly less in the sitagliptin groups compared with the basal bolus group (both P < 0.001). There were no differences in length of hospital stay (P = 0.78) or in the number of hypoglycemic events between groups (P = 0.86). CONCLUSIONS: Results of this pilot indicate that treatment with sitagliptin alone or in combination with basal insulin is safe and effective for the management of hyperglycemia in general medicine and surgery patients with T2D.

[Insulin analogues: modifications in the structure, molecular and metabolic consequences]. / Análogos de insulina: modificaciones en la estructura, consecuencias moleculares y metabólicas.

Recombinant DNA technology has provided insulin analogues for the treatment of diabetes mellitus, with an efficacy and safety that has improved the treatment of this disease. We briefly review the principal characteristics of the insulin analogues currently available. Both rapid-acting (lispro, aspart and glulisine) and long acting (glargine and determir) insulin analogues are included in this review. We describe the pharmacology of each insulin analogue, their differences with the human insulin, the administration, indication, efficacy and safety. In addition we discussed the main controversies of the use of these insulin analogues. In particular, those related with the risk of cancer and retinopathy, and their use in pregnant women.

Insulin analogues for type 1 diabetes in children and adolescents.

Since insulin is the unique and life-long therapy in type 1 diabetes and classical insulin preparations have certain limitations due to their pharmacokinetic and pharmacodynamic properties, the new insulin analogues aim to eliminate these limitations. Five insulin analogues are commercially available and approved for individuals with type 1 diabetes: three rapid-acting (insulin lispro, insulin aspart and insulin glulisine) and two long-acting insulin analogues (insulin glargine and insulin detemir). According to several studies conducted in children with type 1 diabetes, insulin analogues, due to their structural alterations, offer flexibility, reduction of nocturnal hypoglycemic episodes and decrease in postprandial hyperglycemic events, resulting in improved quality of life for diabetic children and their families. However, diabetes control measured with glycosylated hemoglobin A1c has been reported to be similar to conventional insulin preparations. Evidence-based medical reports indicate that insulin analogues are safe and effective, and therefore approved for children even from the age of 2 years. Moreover, suspicions and reports on the association of insulin analogues with carcinogenesis have not been established, requiring further investigation. This review reports the properties and characteristics of insulin analogues, as well as the results of current studies concerning pediatric patients with type 1 diabetes.

Use of neutral protamine lispro (NPL) insulin in a patient affected by acute pancreatitis under parenteral nutrition.

Hyperglycaemia is considered the main obstacle to the activation of a correct nutritional support, even in patients not affected by diabetes mellitus. The stress associated with the acute pathology stimulates controinsular hormones and causes modifications in the glucidic metabolism. Artificial nutrition (AN), both enteral and parenteral (PN), is considered one of the main causes of hyperglycaemia in hospitalized patients. ADI-AMD recommendations underline that a long-acting insulin analogues can be used on a stabilized patient supported with PN via peristaltic pump. In the following case report, a patient under PN was given, after a surgery for acute pancreatitis, an injectable suspension of lispro NPL insulin. Our case report shows that also NPL lispro insulin subcutaneously can be used in patients under PN who need an insulin treatment and who can use a constant-flow infusion pump. Thanks to initial observations on the use of NPL insulin lispro in patients under PN we can assume the importance of such an insulin in association with AN. Clin Ter 2011; 162(3):231-234.