Exploring early combination strategy in Latin American patients with newly diagnosed type 2 diabetes: a sub-analysis of the VERIFY study

Abstract Background Patients with type 2 diabetes mellitus (T2DM) from Latin American countries face challenges in access to healthcare, leading to under-diagnosis, under-achievement of glycemic target, and long-term complications. Early diagnosis and treatment initiation are of paramount importance in this population due to the high prevalence of risk factors such as obesity and metabolic syndrome. The VERIFY study in patients with newly diagnosed T2DM (across 34 countries), assessed the normoglycemic durability (5 years), with early combination (EC) therapy approach versus the traditional stepwise approach of initiating treatment with metformin monotherapy (MET). Here we present the results from the VERIFY study for participants from eight countries in Latin America. Methods Newly diagnosed adult patients with T2DM, HbA1c 6.5–7.5% and body-mass index (BMI) of 22–40 kg/m2 were enrolled. The primary endpoint was time to initial treatment failure (TF; HbA1c ≥ 7.0% at two consecutive scheduled visits 13 weeks apart). Time to second TF was evaluated when patients in both groups were receiving and failing on the vildagliptin combination. Safety and tolerability were also assessed for both treatment approaches during the study. Results A total of 537 eligible patients (female, 58.8%) were randomly assigned to receive either EC (n = 266) or MET (n = 271). EC significantly reduced the relative risk of time to initial TF by 47% versus MET [HR (95% CI) 0.53 (0.4, 0.7) p < 0.0001]. Overall, 46.4% versus 66.3% of patients achieved the primary endpoint in the EC and MET groups, with a median [interquartile range (IQR)] time to TF of 59.8 (27.5, not evaluable) and 33.4 (12.2, 60.1) months, respectively. The risk for time to second TF was 31% lower with EC (p < 0.0092). A higher proportion of patients receiving EC maintained durable HbA1c < 7.0%, < 6.5%, and < 6.0%. Both treatment approaches were well tolerated, and only 3.2% of participants discontinued the study due to adverse events. All hypoglycemic events (EC: n = 7 and MET: n = 3) were single, mild episodes and did not lead to study discontinuation. Conclusion Similar to the global population, long-term clinical benefits were achieved more frequently and without tolerability issues with EC versus standard-of-care MET in this Latin American sub-population. This study is registered with ClinicalTrials.gov, NCT01528254.

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Exploring Early Combination Strategy in Latin American Patients With Newly Diagnosed Type 2 Diabetes: A Sub-analysis of the VERIFY Study

10.21203/rs.3.rs-231231/v1 ◽

2021 ◽

Author(s):

Sergio Vencio ◽

Juan P Manosalva ◽

Chantal Mathieu ◽

Pieter Proot ◽

Hernan Yupanqui Lozno ◽

...

Keyword(s):

Type 2 Diabetes ◽

Latin American ◽

Primary Endpoint ◽

Standard Of Care ◽

Newly Diagnosed ◽

Combination Strategy ◽

Treatment Approaches ◽

Clinical Benefits

Abstract Background: Patients with type 2 diabetes mellitus (T2DM) from Latin American countries face challenges in access to healthcare, leading to under-diagnosis, under-achievement of glycemic target, and long-term complications. Early diagnosis and treatment initiation are of paramount importance in this population due to the high prevalence of risk factors such as obesity and metabolic syndrome. The VERIFY study in patients with newly diagnosed T2DM (across 34 countries), assessed the normoglycemic durability (5 years), with early combination (EC) therapy approach versus the traditional stepwise approach of initiating treatment with metformin monotherapy (MET). Here we present the results from the VERIFY study for participants from eight countries in Latin America. Methods: Newly diagnosed adult patients with T2DM, HbA1c 6.5%–7.5% and body-mass index (BMI) of 22–40 kg/m² were enrolled. The primary endpoint was time to initial treatment failure (TF; HbA1c ≥7.0% at two consecutive scheduled visits 13 weeks apart). Time to second TF was evaluated when patients in both groups were receiving and failing on the vildagliptin combination. Safety and tolerability were also assessed for both treatment approaches during the study.Results: A total of 537 eligible patients (female, 58.8%) were randomly assigned to receive either EC (n=266) or MET (n=271). EC significantly reduced the relative risk of time to initial TF by 47% versus MET (HR [95% CI] 0.53 [0.4, 0.7]; p<0.0001). Overall, 46.4% versus 66.3% of patients achieved the primary endpoint in the EC and MET groups, with a median (interquartile range [IQR]) time to TF of 59.8 (27.5, not evaluable) and 33.4 (12.2, 60.1) months, respectively. The risk for time to second TF was 31% lower with EC (p<0.0092). A higher proportion of patients receiving EC maintained durable HbA1c <7.0%, <6.5%, and <6.0%. Both treatment approaches were well tolerated, and only 3.2% of participants discontinued the study due to adverse events. All hypoglycemic events (EC: n=7 and MET: n=3) were single, mild episodes and did not lead to study discontinuation. Conclusion: Similar to the global population, long-term clinical benefits were achieved more frequently and without tolerability issues with EC versus standard-of-care MET in this Latin American sub-population.This study is registered with ClinicalTrials.gov, NCT01528254.

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Long-term clinical benefits with early combination therapy in patients with newly diagnosed type 2 diabetes from Europe: insights from the VERIFY study

Endocrine Abstracts ◽

10.1530/endoabs.73.pep2.4 ◽

2021 ◽

Author(s):

Cos Francesc Xavier ◽

Emanuele Bosi ◽

Piermarco Piatti ◽

Päivi M Paldánius

Keyword(s):

Type 2 Diabetes ◽

Combination Therapy ◽

Newly Diagnosed ◽

Clinical Benefits ◽

Early Combination Therapy

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2325-PUB: Estimation Formula for the Long-Term Glycemic Remission in Patients with Newly Diagnosed Type 2 Diabetes Receiving Short-Term Intensive Insulin Therapy

Diabetes ◽

10.2337/db19-2325-pub ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 2325-PUB

Author(s):

LIJUAN XU ◽

LIEHUA LIU ◽

XUESI WAN ◽

ZHIMIN HUANG ◽

YANBING LI

Keyword(s):

Type 2 Diabetes ◽

Insulin Therapy ◽

Intensive Insulin Therapy ◽

Newly Diagnosed ◽

Short Term ◽

Estimation Formula

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Clinical Characteristics and Risk of Diabetic Complications in Data-Driven Clusters Among Type 2 Diabetes

Frontiers in Endocrinology ◽

10.3389/fendo.2021.617628 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lin Xing ◽

Fangyu Peng ◽

Qian Liang ◽

Xiaoshuang Dai ◽

Junli Ren ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Complications ◽

Clinical Characteristics ◽

Chinese Patients ◽

Newly Diagnosed ◽

Medication Treatment ◽

Dipeptidyl Peptidase 4 ◽

Age Related

BackgroundThis study aimed to cluster newly diagnosed patients and patients with long-term diabetes and to explore the clinical characteristics, risk of diabetes complications, and medication treatment related to each cluster.Research Design and MethodsK-means clustering analysis was performed on 1,060 Chinese patients with type 2 diabetes based on five variables (HbA1c, age at diagnosis, BMI, HOMA2-IR, and HOMA2-B). The clinical features, risk of diabetic complications, and the utilization of elven types of medications agents related to each cluster were evaluated with the chi-square test and the Tukey–Kramer method.ResultsFour replicable clusters were identified, severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). In terms of clinical characteristics, there were significant differences in blood pressure, renal function, and lipids among clusters. Furthermore, individuals in SIRD had the highest prevalence of stages 2 and 3 chronic kidney disease (CKD) (57%) and diabetic peripheral neuropathy (DPN) (67%), while individuals in SIDD had the highest risk of diabetic retinopathy (32%), albuminuria (31%) and lower extremity arterial disease (LEAD) (13%). Additionally, the difference in medication treatment of clusters were observed in metformin (p = 0.012), α-glucosidase inhibitor (AGI) (p = 0.006), dipeptidyl peptidase 4 inhibitor (DPP-4) (p = 0.017), glucagon-like peptide-1 (GLP-1) (p <0.001), insulin (p <0.001), and statins (p = 0.006).ConclusionsThe newly diagnosed patients and patients with long-term diabetes can be consistently clustered into featured clusters. Each cluster had significantly different patient characteristics, risk of diabetic complications, and medication treatment.

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Predictors of Long-Term Glycemic Remission After 2-Week Intensive Insulin Treatment in Newly Diagnosed Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-01468 ◽

2019 ◽

Vol 104 (6) ◽

pp. 2153-2162 ◽

Cited By ~ 2

Author(s):

Hui Wang ◽

Jian Kuang ◽

Mingtong Xu ◽

Zhengnan Gao ◽

Qifu Li ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Treatment ◽

Newly Diagnosed ◽

Intensive Insulin Treatment

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Insulin requirement profiles of short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes and its association with long-term glycemic remission

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2015.02.011 ◽

2015 ◽

Vol 108 (2) ◽

pp. 250-257 ◽

Cited By ~ 8

Author(s):

Liehua Liu ◽

Weijian Ke ◽

Xuesi Wan ◽

Pengyuan Zhang ◽

Xiaopei Cao ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Therapy ◽

Intensive Insulin Therapy ◽

Insulin Requirement ◽

Newly Diagnosed ◽

Short Term

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Effect of medication adherence on long-term all-cause-mortality and hospitalization for cardiovascular disease in 65,067 newly diagnosed type 2 diabetes patients

Scientific Reports ◽

10.1038/s41598-018-30740-y ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 7

Author(s):

Yeon-Yong Kim ◽

Jin-Seok Lee ◽

Hee-Jin Kang ◽

Sang Min Park

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Medication Adherence ◽

Newly Diagnosed ◽

All Cause Mortality ◽

Diabetes Patients

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Long-term Trends in Antidiabetes Drug Usage in the U.S.: Real-world Evidence in Patients Newly Diagnosed With Type 2 Diabetes

Diabetes Care ◽

10.2337/dc17-1414 ◽

2017 ◽

Vol 41 (1) ◽

pp. 69-78 ◽

Cited By ~ 81

Author(s):

Olga Montvida ◽

Jonathan Shaw ◽

John J. Atherton ◽

Frances Stringer ◽

Sanjoy K. Paul

Keyword(s):

Type 2 Diabetes ◽

Real World ◽

Newly Diagnosed ◽

Drug Usage ◽

Real World Evidence ◽

Long Term Trends ◽

The U.S

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Curcumin in Autoimmune and Rheumatic Diseases

Nutrients ◽

10.3390/nu11051004 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1004 ◽

Cited By ~ 14

Author(s):

Melissa Yang ◽

Umair Akbar ◽

Chandra Mohan

Keyword(s):

Type 2 Diabetes ◽

Ulcerative Colitis ◽

Clinical Trials ◽

Therapeutic Agent ◽

Standard Of Care ◽

Cohort Size ◽

Lipid Levels ◽

Current Standard

Over recent decades, many clinical trials on curcumin supplementation have been conducted on various autoimmune diseases including osteoarthritis, type 2 diabetes, and ulcerative colitis patients. This review attempts to summarize the highlights from these clinical trials. The efficacy of curcumin either alone or in conjunction with existing treatment was evaluated. Sixteen clinical trials have been conducted in osteoarthritis, 14 of which yielded significant improvements in multiple disease parameters. Eight trials have been conducted in type 2 diabetes, all yielding significant improvement in clinical or laboratory outcomes. Three trials were in ulcerative colitis, two of which yielded significant improvement in at least one clinical outcome. Additionally, two clinical trials on rheumatoid arthritis, one clinical trial on lupus nephritis, and two clinical trials on multiple sclerosis resulted in inconclusive results. Longer duration, larger cohort size, and multiple dosage arm trials are warranted to establish the long term benefits of curcumin supplementation. Multiple mechanisms of action of curcumin on these diseases have been researched, including the modulation of the eicosanoid pathway towards a more anti-inflammatory pathway, and the modulation of serum lipid levels towards a favorable profile. Overall, curcumin supplementation emerges as an effective therapeutic agent with minimal-to-no side effects, which can be added in conjunction to current standard of care.

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