Safety and efficacy of P2Et extract from Caesalpinia spinosa in breast cancer patients: study protocol for a randomized double blind phase II clinical trial (CS003-BC).

BACKGROUND: Chemotherapy in breast cancer is effective but can generate significant toxicity and lead to tumor resistance. Joint treatment with standardized plant extracts can be an alternative to improve the response and allow an effective activation of the antitumor immune response that favors recovery in the short and long term. The P2Et extract of Caesalpinia spinosa presents antitumor activity in cells and animal models of breast cancer, improves the tumor microenvironment, and induces activation of the specific immune response against the tumor and is synergistic when used together with anthracyclines, which makes it a good candidate for evaluation in patients. METHODS: Conducted at a single center, this phase II study is a randomized, double-blind, placebo-controlled trial aimed at assessing the safety and efficacy of P2Et extract in patients diagnosed with stage II and III breast cancer, who are eligible for neoadjuvant treatment. The study aims to determine the safety profile at the previously established optimal biological dose from phase I trial while investigating various efficacy outcomes. These outcomes include improvements in quality of life, immunomodulation, metabolic profile, microbiome, as well as clinical indicators such as tumor reduction, disease-free survival, and pathological response, assessed at different stages of the treatment regimen. DISCUSSION: Treatment with the P2Et extract in breast cancer patients is hypothesized to enhance overall well-being, positively influencing their quality of life, while also triggering an antitumor immune response and enhancing immune infiltration. These combined effects have the potential to contribute to improved long-term survival outcomes for patients receiving the phytomedicine alongside neoadjuvant chemotherapy treatment. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT05007444. First Registered August 16th, 2021. Last Updated: August 9th, 2022.

Exploring the safety and efficacy of phytomedicine Petiveria alliacea extract (Esperanza) in patients with metastatic gastrointestinal tumors and acute leukemias: study protocol for a phase Ib/randomized double blind phase II trial (PA001).

BACKGROUND: The energy metabolism of drug-resistant tumor cells can provide a survival advantage during therapy, and treatment itself may influence metabolic reprogramming. Petiveria alliacea (Traditional name: Anamu) could inhibit glycolysis and OXPHOX modulating tumor metabolism, making it a potential treatment for tumors with altered metabolism. This clinical study aims to evaluate the safety and efficacy of a standardized Anamu phytomedicine called Esperanza in treating gastric tumors and acute leukemias. METHODS: This is a prospective, open label, phase I/ randomized, double-blind single-center phase II study designed to evaluate the safety and efficacy of Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias. In stage 1, the study will determine the MTD and assess safety. In stage 2, safety at the MTD will be evaluated, and the efficacy of Esperanza extract will be explored in both metastatic gastric tumors and acute leukemias. Quality of life improvement will be the primary outcome in the gastric tumor group, while different efficacy outcomes will be assessed in the acute leukemia group. A placebo group will be used for comparison in the gastric tumor group, and a historical control group will be used in the acute leukemia arm. DISCUSSION: This clinical trial aims to evaluate the safety profile of the Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias, while exploring its potential efficacy in conjunction with standard treatment for these pathologies. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT05587088. Registered October 19th, 2022.

Glycemic status and health-related quality of life (HRQOL) in populations at risk of diabetes in two Latin American cities.

PURPOSE: To estimate the health-related quality of life (HRQOL) according to glycemic status, and its relationship with sociodemographic and clinical factors in a population at risk of developing type 2 diabetes (T2D). METHODS: Cross-sectional study, using cluster sampling. Data were collected from 1135 participants over 30 years of age, at risk of developing T2D from the PREDICOL project. Participants' glycemic status was defined using an oral glucose tolerance test (OGTT). Participants were divided into normoglycemic subjects (NGT), prediabetes and diabetics do not know they have diabetes (UT2D). HRQOL was assessed using the EQ-5D-3L questionnaire of the EuroQol group. Logistic regression and Tobit models were used to examine factors associated with EQ-5D scores for each glycemic group. RESULTS: The mean age of participants was 55.6 ± 12.1 years, 76.4% were female, and one in four participants had prediabetes or unknown diabetes. Participants reported problems most frequently on the dimensions of Pain/Discomfort and Anxiety/Depression in the different glycemic groups. The mean EQ-5D score in NGT was 0.80 (95% CI 0.79-0.81), in prediabetes, 0.81 (95% CI 0.79-0.83), and in participants with UT2D of 0.79 (95% CI 0.76-0.82), respectively. Female sex, older age, city of residence, lower education, receiving treatment for hypertension, and marital status were significantly associated with lower levels of HRQOL in the Tobit regression analysis. CONCLUSIONS: HRQOL of NGT, prediabetes, and UT2D participants was statistically similar. However, factors such as gender, age. and place of residence were found to be significant predictors of HRQOL for each glycemic group.

The impact of the COVID-19 pandemic on diabetes services: planning for a global recovery.

The COVID-19 pandemic has disproportionately affected certain groups, such as older people (ie, >65 years), minority ethnic populations, and people with specific chronic conditions including diabetes, cardiovascular disease, kidney disease, and some respiratory diseases. There is now evidence of not only direct but also indirect adverse effects of COVID-19 in people with diabetes. Recurrent lockdowns and public health measures throughout the pandemic have restricted access to routine diabetes care, limiting new diagnoses, and affecting self-management, routine follow-ups, and access to medications, as well as affecting lifestyle behaviours and emotional wellbeing globally. Pre-pandemic studies have shown that short-term delays in delivery of routine care, even by 12 months, are associated with adverse effects on risk factor control and worse microvascular, macrovascular, and mortality outcomes in people with diabetes. Disruptions within the short-to-medium term due to natural disasters also result in worse diabetes outcomes. However, the true magnitude of the indirect effects of the COVID-19 pandemic on long-term outcomes and mortality in people with diabetes is still unclear. Disasters tend to exacerbate existing health disparities; as we recover ambulatory diabetes services in the aftermath of the pandemic, there is an opportunity to prioritise those with the greatest need, and to target resources and interventions aimed at improving outcomes and reducing inequality.

Randomized double-blind clinical study in patients with COVID-19 to evaluate the safety and efficacy of a phytomedicine (P2Et).

Background: It has been proposed that polyphenols can be used in the development of new therapies against COVID-19, given their ability to interfere with the adsorption and entrance processes of the virus, thus disrupting viral replication. Seeds from Caesalpinia spinosa, have been traditionally used for the treatment of inflammatory pathologies and respiratory diseases. Our team has obtained an extract called P2Et, rich in polyphenols derived from gallic acid with significant antioxidant activity, and the ability to induce complete autophagy in tumor cells and reduce the systemic inflammatory response in animal models. Methods: In this work, a phase II multicenter randomized double-blind clinical trial on COVID-19 patients was designed to evaluate the impact of the P2Et treatment on the clinical outcome and the immunological parameters related to the evolution of the disease. The Trial was registered with the number No. NCT04410510*. A complementary study in an animal model of lung fibrosis was carried out to evaluate in situ lung changes after P2Et in vivo administration. The ability of P2Et to inhibit the viral load of murine and human coronaviruses in cellular models was also evaluated. Results: Patients treated with P2Et were discharged on average after 7.4 days of admission vs. 9.6 days in the placebo group. Although a decrease in proinflammatory cytokines such as G-CSF, IL-15, IL-12, IL-6, IP10, MCP-1, MCP-2 and IL-18 was observed in both groups, P2Et decreased to a greater extent G-CSF, IL-6 and IL-18 among others, which are related to lower recovery of patients in the long term. The frequency of T lymphocytes (LT) CD3+, LT double negative (CD3+CD4-CD8-), NK cells increased in the P2Et group where the population of eosinophils was also significantly reduced. In the murine bleomycin model, P2Et also reduced lung inflammation and fibrosis. P2Et was able to reduce the viral replication of murine and human coronaviruses in vitro, showing its dual antiviral and anti-inflammatory role, key in disease control. Conclusions: Taken together these results suggest that P2Et could be consider as a good co-adjuvant in the treatment of COVID-19. Clinical trail registration: https://clinicaltrials.gov/ct2/show/NCT04410510, identifier: NCT04410510.

Health-related quality of life (HRQoL) in a population at risk of type 2 diabetes: a cross-sectional study in two Latin American cities.

PURPOSE: The purpose of this study was to describe the health-related quality of life (HRQoL) characteristics in a population at risk of developing type 2 diabetes in Barranquilla and Bogotá, Colombia. METHODS: A cross-sectional study with 1135 participants older than 30 years-of-age recruited in Bogotá D.C., and Barranquilla by cluster sampling in 2018 to 2019. The Finnish Diabetes Risk Score (FINDRISC) was used to detect participants at risk of developing type 2 diabetes (T2D). HRQoL was assessed using the EQ-5D-3L questionnaire. Unadjusted and adjusted logistic regression models were used to calculate odds ratios (OR) and their corresponding 95% confidence intervals CI). RESULTS: Moderate or extreme problems appeared more frequently in the dimensions of Pain/Discomfort (60.8%) and Anxiety/Depression (30.8%). The mean score of the EQ-VAS was 74.3 (± 17.3), significantly larger in the state of complete health (11111) compared with those with problems in more than one of the quality-of-life dimensions. Being female and living in Bogota D.C., were associated with greater odds of reporting problems in the Pain (OR 1.6; 95% CI 1.2-2.2) and Discomfort dimensions (OR 1.6; 95% CI 1.2-2.0) respectively and Anxiety/Depression (OR 1.9; 95% CI 1.3-2.7), (OR 9.1; 95% CI 6.6-12.4), respectively. CONCLUSIONS: As living place and sex were associated with dimensions of Pain/Discomfort and Anxiety/Depression in the HRQoL in people at risk of T2D, greater attention should be paid to these determinants of HRQoL to design and reorient strategies with a territorial and gender perspective to achieve better health outcomes. Diabetes is one of the four non-communicable diseases with increasing prevalence in the world, which has made it a serious public health problem. In Colombia, in 2019 diabetes affected 8.4% of the Colombian adult population and more than one million Colombian adults of this age group have hidden or undetected diabetes. This disease is not only characterized by increased premature mortality, loss of productivity, and economic impact, but it also involves a deterioration in the quality of life of people with diabetes with their respective families. However, very Little is known about health-related quality of life (HRQoL) in a population at risk or with prediabetes. This study has evaluated the quality of life in patients at risk of diabetes and their behavior with some variables as sociodemographic, lifestyle, history, and established their difference in two territories of the Colombian Caribbean. The results of this study indicate that the HRQoL of people at risk of type 2 diabetes is affected by factors such as gender, city, dysglycemia, medication for hypertension and education level. Therefore, greater attention should be paid to these determinants of HRQL to design and implement strategies that reduce this risk of developing type 2 diabetes, prevent prediabetes and improve the quality of life in prediabetic or diabetic patients.

Comparative efficacy and safety of basal insulins: A review.

BACKGROUND AND AIM: To provide an update on the usefulness of basal insulin in patients with type 2 diabetes mellitus. METHODS: We conducted a literature search using PubMed and MEDLINE, BIOSIS, Scopus, EMBASE, ClinicalTrials.gov, Google Scholar, and Springer Online Archives Collection until June 2021. RESULTS: All basal insulins are similar in efficacy, with only small differences among them in terms of the risk of hypoglycemia. CONCLUSIONS: For type 2 diabetes mellitus, all basal insulins have a similar efficacy, with some advantage of Glar-300 and Deg-100 in reducing the risk of hypoglycemia compared to Glar-100.

Validation of the Finnish Type 2 Diabetes Risk Score (FINDRISC) with the OGTT in Health Care Practices in Europe.

AIMS: /hypothesis. To determine the best cut-off threshold value of the Finnish Diabetes Risk Score (FINDRISC) for the detection of diabetes and non-diabetic hyperglycaemia in people 35 years or older at primary health care settings in Europe. METHODS: Cross-sectional study in 11,444 adults from primary health care centres using community and opportunistic screening approaches. All participants completed the FINDRISC questionnaire and underwent a 2-hour oral glucose tolerance test (OGTT). The FINDRISC performance was assessed by the area under the curve (AUC) using receiver operating characteristics (ROC) analysis. The sensitivity, specificity, Youdens index, positive and negative prediction values for different FINDRISC cut-offs were calculated. RESULTS: The optimal FINDRISC value for detecting both diabetes or glucose impairment in the community - screened sample was 14 point with the associated AUC 0.75,5 (95 %CI 0.73,7-0.77,3). The optimal score in the opportunistic screening sample was 16 with the associated AUC only 0.60,4 (95% CI 0.56, 4-0.64, 4). CONCLUSIONS/INTERPRETATION: The FINDRISC is a non-invasive tool useful for detecting people with unknown diabetes and glucose impairment in people visiting primary health centres in Europe.

One in Seven Insulin-Treated Patients in Developing Countries Reported Poor Persistence with Insulin Therapy: Real World Evidence from the Cross-Sectional International Diabetes Management Practices Study (IDMPS).

INTRODUCTION: Although poor adherence to insulin is widely recognised, periodic discontinuation of insulin may cause more severe hyperglycaemia than poor adherence. We assessed persistence with insulin therapy in patients with type 1 (T1D) or type 2 diabetes (T2D) in developing countries and the reasons for insulin discontinuation. METHODS: The International Diabetes Management Practices Study collected real-world data from developing countries in seven waves between 2005 and 2017. In Wave 7 (2016-2017), we asked adult patients with T1D and insulin-treated T2D to report whether they had ever discontinued insulin, the estimated duration of discontinuation and underlying reasons. RESULTS: Among 8303 patients recruited from 24 countries by 620 physicians, 4596 were insulin-treated (T1D: 2000; T2D: 2596). In patients with T1D, 14.0% (95% CI: 12.5-15.6) reported having self-discontinued insulin for a median duration of 1.0 month (IQR: 0.5, 3.5). The respective figures in patients with T2D were 13.7% (12.4-15.1) and 2.0 months (IQR: 1.0, 6.0). The main reasons for discontinuation were impact on social life (T1D: 41.0%; T2D: 30.5%), cost of medications and test strips (T1D: 34.4%; T2D: 24.5%), fear of hypoglycaemia (T1D: 26.7%; T2D: 28.0%) and lack of support (T1D: 26.4%; T2D: 25.9%). Other factors included age < 40 years, non-university education and short disease duration (T1D: ≤ 1 year; T2D: > 1-≤ 5 years). Patients with T1D who did not perform self-monitoring of blood glucose (SMBG) or self-adjust their insulin dosage, and patients with T1D or T2D without glucose meters were less likely to persist with insulin. Nearly 50% of patients who reported poor persistence had HbA1c > 75 mmol/mol (> 9%) and > 50% of physicians recommended diabetes education programmes to improve treatment persistence. CONCLUSION: In developing countries, poor persistence with insulin is common among insulin-treated patients, supporting calls for urgent actions to ensure easy access to insulin, tools for SMBG and education.

High Prevalence of Depressive Symptoms in Patients With Type 1 and Type 2 Diabetes in Developing Countries: Results From the International Diabetes Management Practices Study.

OBJECTIVE: Depression is common in people with diabetes, but data from developing countries are scarce. We evaluated the prevalence and risk factors for depressive symptoms in patients with diabetes using data from the International Diabetes Management Practices Study (IDMPS). RESEARCH DESIGN AND METHODS: IDMPS is an ongoing multinational, cross-sectional study investigating quality of care in patients with diabetes in real-world settings. Data from wave 5 (2011), including 21 countries, were analyzed using the 9-item Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. Logistic regression analyses were conducted to identify risk factors of depressive symptoms. RESULTS: Of 9,865 patients eligible for analysis, 2,280 had type 1 and 7,585 had type 2 diabetes (treatment: oral glucose-lowering drugs [OGLD] only, n = 4,729; OGLDs plus insulin, n = 1,892; insulin only, n = 964). Depressive symptoms (PHQ-9 score ≥5) were reported in 30.7% of those with type 1 diabetes. In patients with type 2 diabetes, the respective figures were 29.0% for OGLDs-only, 36.6% for OGLDs-plus-insulin, and 46.7% for insulin-only subgroups. Moderate depressive symptoms (PHQ-9 score 10-19) were observed in 8-16% of patients with type 1 or type 2 diabetes. Female sex, complications, and low socioeconomic status were independently associated with depressive symptoms. In type 1 diabetes and in the type 2 diabetes OGLDs-only group, depression was associated with poor glycemic control. CONCLUSIONS: Depressive symptoms are common in patients with diabetes from developing countries, calling for routine screening, especially in high-risk groups, to reduce the double burden of diabetes and depression and their negative interaction.

Glycemic Control and Prevention of Diabetic Complications in Low- and Middle-Income Countries: An Expert Opinion.

INTRODUCTION: Trends on glycemic control and diabetes complications are known for high-income countries, but comprehensive data from low- and middle-income countries (LMIC) are lacking. METHODS: This is an expert opinion based on two retrospective studies. Here we examine the recent subset analysis of relevant data from the IDMPS Wave 7 (International Diabetes Management-Practices Study, 2015-2016) and the GOAL study conducted in multiple LMICs. RESULTS: Wave 7 sub-analysis was performed in 6113 people with type 2 diabetes from 24 LMIC. Poorly controlled diabetes (hemogloblin A1c [HbA1c] ≥ 7%) was found in 58.6, 73.0 and 78.3% of participants with diabetes duration of < 5, 5-12 and > 12 years, respectively (in association with a high prevalence of macro- and microvascular complications). Moreover, 37.7% of participants with diabetes duration of 5-12 years were treated only with oral antihyperglycemic drugs. The GOAL study investigated the efficacy of insulin in 2704 poorly controlled participants (mean HbA1c 9.7%; diabetes duration 10.1 ± 6.7 years; 10 LMIC). A significant 2% reduction in mean HbA1c levels was observed after 12 months of treatment. Only 7.2% of participants experienced a symptomatic episode of hypoglycemia (nocturnal or severe hypoglycemia events were infrequent). CONCLUSION: The rate of well-controlled participants (HbA1c < 7.0%) in the Wave 7 sub-analysis was lower than that observed in the USA (NHANES survey) or in European countries (GUIDANCE study), and the incidence of microvascular complications was higher. The GOAL study showed that insulin treatment improves glycemic control and reduces this gap. The Expert Panel recommends intensifying diabetes treatment as soon as possible, as well as patients' education and other preventive measures, initiatives which require modest costs compared to hospitalization and treatment of diabetes complications.

Glycemic control metrics using flash glucose monitoring and hospital complications in patients with COVID-19.

BACKGROUND AND AIMS: Few studies have reported on the use of continuous glucose monitoring (CGM) during the Covid-19 pandemic. We aimed to examine glycemic control metrics using flash glucose monitoring during insulin treatment and the clinical outcome in hospitalized patients with COVID-19. METHODS: Prospective, single-center cohort of adult patients diagnosed with type 2 diabetes or hyperglycemia and COVID-19 infection treated with basal bolus insulin regimen. Glycemic control was assessed with the use of intermittent Freestyle Libre flash glucose monitoring during the hospital stay. Outcome of interest were time in range [TIR], time above [TAR] and below [TBR] range, glycemic variability [coefficient of variation [% CV]), and differences in a composite of complications including ICU admission, acute respiratory distress syndrome (ARDS) and acute kidney injury. RESULTS: A total of 60 patients were included (44 known diabetes and 16 new onset hyperglycemia). In total 190,080 data points of CGM were available, of which 72.5% of values were within the target area [TIR (70-180 mg/dL)], 22% TAR (>180 mg/dL), and 3% were TBR (<70 mg/dL). During treatment, the coefficient of variation (% CV) was 30%. There were no association with TIR, but patients with TAR >180 mg/dl had higher rates of a composite of complications (22.5% vs 16%, p = 0.04). CONCLUSIONS: Basal bolus insulin regimen was safe and effective in achieving inpatient glycemic control in most patients with COVID-19. The association between TAR and complications indicates the need for improved inpatient glycemic control in hospitalized patients with COVID-19.

Screening, prevalence, treatment and control of kidney disease in patients with type 1 and type 2 diabetes in low-to-middle-income countries (2005-2017): the International Diabetes Management Practices Study (IDMPS).

AIMS/HYPOTHESIS: Diabetes is the leading cause of kidney disease worldwide. There is limited information on screening, treatment and control of kidney disease in patients with diabetes in low-to-middle-income countries (LMICs). METHODS: The International Diabetes Management Practices Study is an ongoing, non-interventional study of clinical profiles and practices among patients receiving outpatient care mainly by internal medicine physicians and endocrinologists in LMICs. We examined screening, prevalence, treatment and control of kidney disease across seven waves (W) of data collection between 2005 and 2017. RESULTS: Among 15,079 patients with type 1 and 66,088 patients with type 2 diabetes, screening for kidney disease increased between W2 and W3 followed by a plateau (type 1 diabetes: W2, 73.7%; W3, 84.1%; W7, 83.4%; type 2 diabetes: W2, 65.1%; W3, 82.6%; W7, 86.2%). There were also decreasing proportions of patients with microalbuminuria (type 1 diabetes: W1, 27.1%; W3, 14.7%; W7, 13.8%; type 2 diabetes: W1, 24.5%; W3, 12.6%; W7, 11.9%) and proteinuria (type 1 diabetes: W1, 14.2%; W3, 8.7%; W7, 8.2%; type 2 diabetes: W1, 15.6%; W3, 9.3%; W7, 7.6%). Fewer patients were reported as receiving dialysis for both type 1 diabetes (W2, 1.4%; W7, 0.3%) and type 2 diabetes (W2, 0.9%; W7, 0.2%) over time. While there was no change in mean HbA1c or prevalence of diagnosed hypertension (type 1 diabetes: W1, 22.7%; W7, 19.9%; type 2 diabetes: W1, 60.9%; W7, 66.2%), the use of statins had increased among patients diagnosed with dyslipidaemia (type 1 diabetes: W1, 77.7%; W7, 90.7%; type 2 diabetes: W1, 78.6%; W7, 94.7%). Angiotensin II receptor blockers (type 1 diabetes: W1, 18.0%; W7, 30.6%; type 2 diabetes: W1, 24.2%; W7, 43.6%) were increasingly used over ACE inhibitors after W1 (type 1 diabetes: W1, 65.0%; W7, 55.9%; type 2 diabetes: W1, 55.7%, W7, 41.1%) among patients diagnosed with hypertension. CONCLUSIONS/INTERPRETATION: In LMICs, real-world data suggest improvement in screening and treatment for kidney disease in patients with type 1 and type 2 diabetes attending non-nephrology clinics. This was accompanied by decreasing proportions of patients with microalbuminuria and proteinuria, with fewer patients who reported receiving dialysis over a 12-year period.

Obesity and COVID-19 in Latin America: A tragedy of two pandemics-Official document of the Latin American Federation of Obesity Societies.

In May 2020, Latin America became the epicenter of the COVID-19 pandemic, a region already afflicted by social disparities, poor healthcare access, inadequate nutrition and a large prevalence of noncommunicable chronic diseases. Obesity and its comorbidities are increasingly prevalent in Latin America, with a more rapid growth in individuals with lower income, and currently a disease associated with COVID-19 severity, complications and death. In this document, the Latin American Association of Obesity Societies and collaborators present a review of the burden of two pandemics in Latin America, discuss possible mechanisms that explain their relationship with each other and provide public health and individual recommendations, as well as questions for future studies.

Cambios en la incidencia de diabetes mellitus tipo 1 en menores de 15 años en la ciudad de Bogotá, Colombia / Changes in the incidence of diabetes mellitus type 1 in children under the age of 15 in the city of Bogotá, Colombia

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Correction to: Persistent poor glycaemic control in individuals with type 2 diabetes in developing countries: 12 years of real-world evidence of the International Diabetes Management Practices Study (IDMPS).

Unfortunately, the standard deviations for 'last HbA1c measurement' in mmol/mol were miscalculated in Table 1 of this paper.

Persistent poor glycaemic control in individuals with type 2 diabetes in developing countries: 12 years of real-world evidence of the International Diabetes Management Practices Study (IDMPS).

AIMS/HYPOTHESIS: We evaluated the secular trend of glycaemic control in individuals with type 2 diabetes in developing countries, where data are limited. METHODS: The International Diabetes Management Practices Study provides real-world evidence of patient profiles and diabetes care practices in developing countries in seven cross-sectional waves (2005-2017). At each wave, each physician collected data from ten consecutive participants with type 2 diabetes during a 2 week period. The primary objective of this analysis was to evaluate trends of glycaemic control over time. RESULTS: A total of 66,088 individuals with type 2 diabetes were recruited by 6099 physicians from 49 countries. The proportion of participants with HbA1c <53 mmol/mol (<7%) decreased from 36% in wave 1 (2005) to 30.1% in wave 7 (2017) (p < 0.0001). Compared with wave 1, the adjusted ORs of attaining HbA1c ≤64 mmol/mol (≤8%) decreased significantly in waves 2, 5, 6 and 7 (p < 0.05). Over 80% of participants received oral glucose-lowering drugs, with declining use of sulfonylureas. Insulin use increased from 32.8% (wave 1) to 41.2% (wave 7) (p < 0.0001). The corresponding time to insulin initiation (mean ± SD) changed from 8.4 ± 6.9 in wave 1 to 8.3 ± 6.6 years in wave 7, while daily insulin dosage ranged from 0.39 ± 0.21 U/kg (wave 1) to 0.33 ± 0.19 U/kg (wave 7) for basal regimen and 0.70 ± 0.34 U/kg (wave 1) to 0.77 ± 0.33 (wave 7) U/kg for basal-bolus regimen. An increasing proportion of participants had ≥2 HbA1c measurements within 12 months of enrolment (from 61.8% to 92.9%), and the proportion of participants receiving diabetes education (mainly delivered by physicians) also increased from 59.0% to 78.3%. CONCLUSIONS: In developing countries, glycaemic control in individuals with type 2 diabetes remained suboptimal over a 12 year period, indicating a need for system changes and better organisation of care to improve self-management and attainment of treatment goals.

Insulin Therapy in Type 2 Diabetes.

BACKGROUND: Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But even with the availability of oral glucose-lowering drugs, insulin supplementation was often needed to achieve good glucose control in type 2 diabetes. Insulin NPH became the basal insulin therapy of choice and adding NPH to metformin and/or sulfonylureas became the standard of care until basal insulin analogs were developed and new glucose-lowering drugs became available. AREAS OF UNCERTAINTY: The advantages in cost-benefit of insulin analogs and their combination with new glucose-lowering drugs are still a matter of debate. There is no general agreement on how to avoid inertia by prescribing insulin therapy in type 2 diabetes when really needed, as reflected by the diversity of recommendations in the current clinical practice guidelines. DATA SOURCES: When necessary for this review, a systematic search of the evidence was done in PubMed and Cochrane databases. THERAPEUTIC ADVANCES: Adding new oral glucose-lowering drugs to insulin such as DPP-4 inhibitors lead to a modest HbA1c reduction without weight gain and no increase in hypoglycemia. When SGLT-2 inhibitors are added instead, there is a slightly higher HbA1c reduction, but with body weight and blood pressure reduction. The downside is the increase in genital tract infections. GLP-1 receptor agonists have become the best alternative when basal insulin fails, particularly using fixed ratio combinations. Rapid-acting insulins via the inhaled route may also become an alternative for insulin supplementation and/or intensification. "Smart insulins" are under investigation and may become available for clinical use in the near future. CONCLUSIONS: Aggressive weight loss strategies together with the new glucose-lowering drugs which do not cause hypoglycemia nor weight gain should limit the number of patients with type 2 diabetes needing insulin. Nevertheless, because of therapeutic inertia and the progressive nature of the disease, many need at least a basal insulin supplementation and insulin analogs are the best choice as they become more affordable. Fixed ratio combinations with GLP1 receptor agonists are a good choice for intensification of insulin therapy.