Personalized Diabetes Medication Adjustment for Type 2 Diabetes
(CHANGE Trial)
Recruiting in Palo Alto (17 mi)
Overseen byMary K Rhee, MD, MSCR
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Waitlist Available
Sponsor: Foundation for Atlanta Veterans Education and Research, Inc.
No Placebo Group
Trial Summary
What is the purpose of this trial?Diabetes is a disorder of high blood glucose, that tends to get worse; over time, patients need more and more drugs. This pattern is caused by overwork of the body's insulin-producing β-cells, because patients' glucose levels are typically above normal; if the investigators kept glucose levels normal - reducing β-cell work - the investigators might be able to keep the disease from getting worse. This trial is aimed to show that adjusting the drugs to keep glucose levels normal, can help to preserve β-cell function compared to usual diabetes care, possibly reduce the tendency to develop the eye and kidney complications of diabetes, and might also be more cost-effective than usual care.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators.
What data supports the idea that Personalized Diabetes Medication Adjustment for Type 2 Diabetes is an effective treatment?
The available research shows that using a combination of drugs like linagliptin and metformin can be more effective than using just one drug alone. This combination helps people with type 2 diabetes manage their blood sugar levels better, especially those with higher initial levels. Additionally, empagliflozin, a type of drug used in these personalized adjustments, has shown better long-term control of blood sugar compared to some other drugs. These findings suggest that personalized medication adjustments can be a successful approach for managing type 2 diabetes.
12345What safety data exists for personalized diabetes medication adjustment for Type 2 Diabetes?
The safety data for personalized diabetes medication adjustment, which includes drugs like metformin, dapagliflozin, semaglutide, saxagliptin, empagliflozin, linagliptin, and canagliflozin, shows that these medications generally have a favorable safety profile. Combination therapies such as saxagliptin and dapagliflozin are noted for their benefits in glycemic control without significant risks of weight gain or hypoglycemia. Saxagliptin/metformin combinations are considered safe for patients with cardiovascular disease, elderly patients, and those with impaired renal function, with few adverse events reported. Semaglutide has shown high efficacy in lowering HbA1c with a safety profile similar to other antidiabetic agents, primarily causing gastrointestinal side effects. Overall, these medications are considered safe with manageable side effects, making them suitable for personalized diabetes management.
46789Is adjusting diabetes medication based on glucose levels a promising treatment for type 2 diabetes?
Yes, adjusting diabetes medication based on glucose levels is promising because it can be personalized to fit individual needs, potentially improving diabetes management and helping patients achieve better blood sugar control.
310111213Eligibility Criteria
This trial is for adults aged 40-74 with Type 2 Diabetes, having specific glucose levels and HbA1c between 6.0-7.4%. It's not for those who've had bariatric surgery, severe kidney issues, dementia, recent heart problems or pancreatitis, are pregnant or extremely overweight.Inclusion Criteria
Your blood sugar level after drinking a sugary drink is higher than 155 mg/dl.
I am between 40 and 74 years old.
You have been diagnosed with diabetes through an oral glucose tolerance test (OGTT).
+1 more
Exclusion Criteria
I have pancreatitis.
I have a family or personal history of MEN2A.
I am currently taking steroid medications.
+10 more
Participant Groups
The study tests if adjusting diabetes medication to maintain normal glucose levels can preserve insulin-producing cell function better than usual care based on HbA1c levels alone. This could slow disease progression and prevent complications.
2Treatment groups
Experimental Treatment
Active Control
Group I: USE OF DIABETES Rx GUIDED BY SELF-MONITORED BLOOD GLUCOSE (SMBG)Experimental Treatment1 Intervention
1. Guidance by SMBG:
2. Glucose goals: We will aim for \<100 mg/dl premeal (2), \<130 postmeal.
3. Monitoring will include pre-breakfast 2x/wk, and a 5-point profile 1x/wk (before and 1.5-2.5 hr after breakfast, before lunch, before supper, and bedtime).
4. Added Rx will be used if SMBG is \>goal ≥3x in 2 consecutive weeks after ≥4 weeks of MOVE! and/or the previous Rx \[e.g., any 3 of the 7 goals (\<100 mg/dl premeal, \<130 post)\]. Metformin ER will be given first (if not already on it), and increased to 2000 mg/day if there are no side effects. (If metformin is not tolerated, it will be stopped and the second Rx will become the "first Rx" and given instead. If other Rx are not tolerated, the next Rx will be used. The second Rx will be the TZD pioglitazone, followed by the GLP-1 RA semaglutide, then the SGLT-2 inhibitor empagliflozin. If still above goal, glargine insulin will be added, titrated to keep fasting glucose \<100 mg/dl.
Group II: USE OF DIABETES Rx GUIDED LARGELY BY HbA1c LEVELSActive Control1 Intervention
Extended-release \[ER\] metformin will be added if HbA1c is ≥7.0% after 3 months; if already used and maximized, pioglitazone will be begun. Other Rx will be added each time HbA1c reaches ≥7.5%. The sequence of Rx will be the same as in intensive Rx subjects; those using insulin will also do prebreakfast SMBG, aiming for glucose \<100 mg/dl.
Intensification of diabetes medication based largely on HbA1c levels is already approved in European Union, United States, United States, European Union, Canada, Japan, China for the following indications:
🇪🇺 Approved in European Union as Metformin for:
- Type 2 diabetes mellitus
🇺🇸 Approved in United States as Dapagliflozin for:
- Type 2 diabetes mellitus
- Heart failure
- Chronic kidney disease
🇺🇸 Approved in United States as Semaglutide for:
- Type 2 diabetes mellitus
- Weight management
🇪🇺 Approved in European Union as Saxagliptin for:
- Type 2 diabetes mellitus
🇨🇦 Approved in Canada as Empagliflozin for:
- Type 2 diabetes mellitus
- Heart failure
🇯🇵 Approved in Japan as Linagliptin for:
- Type 2 diabetes mellitus
🇨🇳 Approved in China as Canagliflozin for:
- Type 2 diabetes mellitus
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Atlanta VA Medical CenterDecatur, GA
Loading ...
Who Is Running the Clinical Trial?
Foundation for Atlanta Veterans Education and Research, Inc.Lead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
Emory UniversityCollaborator
Abbott Diabetes CareIndustry Sponsor
References
Managing hyperglycemia in patients with type 2 diabetes mellitus: rationale for the use of dipeptidyl peptidase-4 inhibitors in combination with other oral antidiabetic drugs. [2010]Type 2 diabetes mellitus is a chronic, progressive disease that necessitates comprehensive and individualized patient treatment strategies. Daily glycemic measures, including measures of postprandial glucose and fasting plasma glucose levels, in combination with measures of glycated hemoglobin (HbA(1c)) levels may be a more reliable indicator of blood glucose control and the long-term risk of complications than measures of HbA(1c) levels alone. Emerging treatment strategies for type 2 diabetes support the rationale for using dipeptidyl peptidase-4 (DPP-4) inhibitors in combination with other oral antidiabetic drugs for early and aggressive management of type 2 diabetes.
Initial combination therapy for patients with type 2 diabetes mellitus: considerations for metformin plus linagliptin. [2021]For patients with type 2 diabetes mellitus, management of hyperglycemia is typically complex, and few patients successfully achieve and maintain recommended targets for glycated hemoglobin (HbA1c). Increasingly, combination therapy is recommended early in the disease course, or even directly at diagnosis in patients with relatively high HbA1c levels. A recent randomized, placebo-controlled, Phase III trial investigated the initial combination of linagliptin and metformin in patients with inadequate glycemic control to assess the benefits of initial combination compared with monotherapy. Linagliptin and metformin act in complementary ways, and the combination treatment showed superior efficacy compared with either monotherapy. Notably, responses were largest in patients with higher baseline HbA1c levels compared with moderate levels, suggesting this combination could be considered in these patients. This may be particularly relevant for those unwilling to start insulin because they prefer oral therapy or need to avoid body weight gain. Neither metformin nor linagliptin is associated with weight gain, and in this trial the combination was also weight neutral. As this combination therapy was well tolerated, with a low frequency of hypoglycemia, these findings suggest that initial combination of linagliptin plus metformin may have advantages for a large proportion of patients in clinical practice.
COMPARING CLINICAL OUTCOMES AND COSTS FOR DIFFERENT TREATMENT INTENSIFICATION APPROACHES IN PATIENTS WITH TYPE 2 DIABETES UNCONTROLLED ON BASAL INSULIN: ADDING GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS VERSUS ADDING RAPID-ACTING INSULIN OR INCREASING BASAL INSULIN DOSE. [2022]Label="OBJECTIVE" NlmCategory="OBJECTIVE">Not all patients with type 2 diabetes achieve recommended glycated hemoglobin A1c (A1C) levels after adequate titration of basal insulin (BI). Current intensification approaches include addition of rapid-acting insulin (RAI) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA), but it is not clear which strategy results in better long-term outcomes.
Long-term efficacy of gliflozins versus gliptins for Type 2 Diabetes after metformin failure: a systematic review and network meta-analysis. [2023]After metformin failure in treatment for diabetes type 2, there is no trivial option for adjuvant medication. The last two oral class medications, gliflozins and gliptins, have different mechanisms of action but have never been compared in long run studies. The aim of the present meta-analysis is to assess the overall long-term efficacy of these drugs after metformin failure. A systematic review and meta-analysis were performed, including all trials with a duration of over 2 years, comparing gliflozins or gliptins after metformin failure in type 2 diabetes. Data Sources: Pubmed (Medline), Embase, Lilacs, and the Cochrane Library from inception through July 2016 without language restrictions. The longest study period found in the literature was 4 years. We selected 1 article on empagliflozin, 1 on dapagliflozin, and 1 on saxagliptin with missing data. After one year of treatment, over 50% of the patients presented HbA1c > 7%. Efficacy rate after 4 years of empagliflozin (23%) was better than dapagliflozin (5%) and saxagliptin (7%); however, it presented statistically non-significant values for HbA1c (7.4 and 7.3% between gliflozins), and missing data for saxaglifozin. Nonetheless, empagliflozin performed better than glimepiride in the 4-year period (standardized mean difference SMD 0.4, confidence interval CI 95% 0.23 to 0.56). The failure of the secondary treatment using gliflozins occurs in less than one year of treatment (less than 50% of the patients presenting HbA1c > 7 %). Empagliflozin offered better glycemic control compared to sulfonylureas but was similar to dapagliflozin.
Patterns and trends in insulin intensification among patients with type 2 diabetes: a systematic review. [2022]Type 2 diabetes (T2DM) diagnoses are skyrocketing, making treatment of this disease an increasing focus of primary care visits. Guidelines recommend insulin intensification over time to achieve HbA1c targets. We conducted a systematic review regarding patterns and trends of insulin intensification and barriers to intensification. Providers across primary and specialty care settings often did not intensify insulin regimens despite patients' clinical status. Even among progressed patients, HbA1c values remained high. The paucity of available studies prevented a comprehensive understanding of patterns and trends in insulin intensification. Such information is needed to assess the quality of pharmacologic care for patients with T2DM.
Combination therapy with saxagliptin and dapagliflozin for the treatment of type 2 diabetes. [2022]Sodium glucose co-transporter 2 (SGLT2) inhibitors such as dapagliflozin and dipeptidyl peptidase-4 (DPP-4) inhibitors such as saxagliptin have the potential to confer significant benefits in glycemic control without the risk of weight gain and hypoglycemia, which may be associated with other medications used to treat type 2 diabetes.
Clinical utility in the treatment of type 2 diabetes with the saxagliptin/metformin fixed combination. [2021]Fixed-dose combination (FDC) products represent a widely accepted approach to type 2 diabetes treatment, given that monotherapies sometimes fail to meet the treatment targets - obtaining a sustained reduction in micro- and macrovascular complications. Saxagliptin (SAXA)/metformin (MET) FDC tablets can be used either alone or in combination with glyburide, thiazolidinediones, or insulin. It has been proven that the SAXA/MET combination leads to a significant improvement in glycemic control compared to placebo in patients with type 2 diabetes that is inadequately controlled with MET alone. In addition, this FDC has been proven to be safe for people with diabetes mellitus and established cardiovascular disease, elderly patients, and patients with impaired renal function (>30 mL/minute), with dosage modification. Patient compliance, adherence, and persistence to the therapeutic regimen has been shown to be very good, while the titration of each compound according to the patient's profile is easy, given the availability of different formulations. The SAXA/MET FDC is a patient-friendly, dosage-flexible, and hypoglycemia-safe regimen with very few adverse events and a neutral or even favorable effect on body weight. It achieves significant glycosylated hemoglobin A1c reduction helping the patient to achieve his/her individual glycemic goals.
Systematic Review of Efficacy and Safety of Newer Antidiabetic Drugs Approved from 2013 to 2017 in Controlling HbA1c in Diabetes Patients. [2020]Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes mellitus and accounts for about 95% of all diabetes cases. Many newer oral as well as parenteral antidiabetic drugs have been introduced in to the market in recent years to control hyperglycemic conditions in diabetes patients and many of these drugs produce potential side effects in diabetes patients. Hence, this systematic review was aimed to analyze and compare the efficacy and safety of oral antidiabetic agents in controlling HbA1c in T2DM patients, that were approved by the United States-Food and Drug Administration (US-FDA) from 2013 to 2017. All randomized controlled, double-blind trials published in English during the search period involving the newer antidiabetic agents were selected. In the outcome assessment comparison, semaglutide demonstrated the highest efficacy in lowering HbA1c, with a 1.6% reduction (p < 0.0001) when given at a dose of 1.0 mg. The safety profile of all the agents as compared to placebo or control were similar, with no or slight increase in the occurrence of adverse events (AEs) but no fatal reaction was reported. The most common AEs of all the antidiabetic agents were gastrointestinal in nature, with several cases of hypoglycemic events. However, among all these agents, semaglutide seems to be the most efficacious drug to improve glycemic control in terms of HbA1c. Alogliptin has the least overall frequency of AEs compared to other treatment groups.
Effects of saxagliptin added to sub-maximal doses of metformin compared with uptitration of metformin in type 2 diabetes: the PROMPT study. [2013]The PROMPT study compared efficacy and tolerability of two treatment intensification strategies: adding saxagliptin or uptitrating metformin monotherapy, in patients with type 2 diabetes (T2D) and inadequate glycaemic control on a sub-maximal metformin dose.
Does personalized diabetology overcome clinical uncertainty and therapeutic inertia in type 2 diabetes? [2022]Uncertainties abound in clinical management of type 2 diabetes. Sources of uncertainty specific to type 2 diabetes originate from the panoply of glycemic (HbA1c) targets, the complexity of drug therapy, the ideal sequence of drugs after metformin failure, the possible harms of anti-hyperglycemic drugs, the outcomes of treatment (surrogate versus clinical) and the hierarchy of risk factors to treat in order to prevent the vascular complications. Ironically, multiple treatment guidelines and algorithms periodically released to improve guidance may generate confusion into clinicians. Moreover, treatment algorithms cannot be truly evidence-based because of a lack of studies comparing all available treatment combination options. Personalized therapy essentially identifies patients who could have major benefits from the therapy as compared with other patients. Personalized medicine for type 2 diabetic has the potential to improve the quality health-care practice of diabetes management, but specific research is needed.
Linagliptin (BI 1356), a potent and selective DPP-4 inhibitor, is safe and efficacious in combination with metformin in patients with inadequately controlled Type 2 diabetes. [2022]The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, linagliptin, added to ongoing metformin therapy, were assessed in patients with Type 2 diabetes who had inadequate glycaemic control (HbA(1c) ≥ 7.5 to ≤ 10%; ≥ 58.5 to ≤ 85.8 mmol/mol) with metformin alone.
Empagliflozin and linagliptin combination therapy for treatment of patients with type 2 diabetes mellitus. [2019]Many patients with type 2 diabetes mellitus (T2DM) fail to achieve the desired A1c goal because the antidiabetic medications used do not correct the underlying pathophysiologic abnormalities and monotherapy is not sufficiently potent to reduce the A1c to the 6.5 - 7.0% range. Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in T2DM. We examine combination therapy with linagliptin plus empagliflozin as a therapeutic approach for the treatment of inadequately controlled T2DM patients.
Predictors of HbA1c treatment response to add-on medication following metformin monotherapy: a population-based cohort study. [2023]Evidence on the influence of patient characteristics on HbA1c treatment response for add-on medications in patients with type 2 diabetes (T2D) is unclear. This study aims to investigate the predictors of HbA1c treatment response for three add-on medications (sulfonylureas (SU), dipeptidyl peptidase-4 (DPP-4) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor) in metformin monotherapy treated patients with T2D. This retrospective cohort study was conducted using the electronic health record data from six primary care clinics in Singapore. A total of 9748 adult patients with T2D on metformin monotherapy receiving SU, DPP-4 or SGLT-2 add-on were 1:1 propensity score matched to patients receiving other add-on medications. Patient demographics, laboratory results, diabetes related complications, comedications, and treatment response at two endpoints (HbA1c reduction ≥ 1% at 6th month, HbA1c goal attainment < 7% at 12th month) were examined. Multiple logistic regression analyses were used to identify patient characteristics associated with the treatment responses. After matching, there were 1073, 517, and 290 paired cohorts of SU, DPP-4 and SGLT-2 respectively. Besides baseline HbA1c, patients with longer hypertension disease duration and higher cholesterol HDL were associated with better treatment response to SU medication add-on. Lower estimated glomerular filtration rate (eGFR), and angiotensin-II receptor medications were associated with better treatment response to DPP-4 add-on. Lower cholesterol HDL, higher creatinine serum, absence of renal complications and beta-blockers medications were associated with better treatment response to SGLT-2 add-on. The cholesterol HDL, creatinine serum, eGFR, hypertension disease duration, angiotensin-II receptors and beta-blockers class of medications can influence the HbA1c treatment response for SU, DPP-4 and SGLT-2 add-on medications. Knowing the patients' characteristics that influence treatment response can assist in guiding clinical decisions when selecting the appropriate add-on medication, ultimately helping to prevent the development of diabetes-related complications.