A Review Of Insulin Resistance In Type 1 Diabetes: Is There A Place For Adjunctive Metformin?
, Volume 9, Issue1 , pp 349361 | Cite as A Review of Insulin Resistance in Type 1 Diabetes: Is There a Place for Adjunctive Metformin? There is a rising trend of overweight and obesity among individuals with type 1 diabetes. This is often associated with insulin resistance, increased insulin dose requirements and poor glycemic control. Insulin resistance is also seen during puberty and is strongly related to increased risk of cardiovascular disease. The role of metformin as an adjunct to ongoing intensive insulin therapy in type 1 diabetics has been evaluated in several randomized trials, including the recently concluded T1D Exchange Network trial in adolescents and the REMOVAL trial in adults. Metformin reduces the insulin dose requirement, insulin-induced weight gain, and total and LDL cholesterol, but results in an increased risk of gastrointestinal adverse effects and a minor increase in the risk of hypoglycemia. In addition, metformin has been shown to reduce maximal carotid intima media thickness and therefore may extend cardioprotective benefits in type 1 diabetes. The role of metformin as adjunctive therapy in type 1 diabetes needs to be explored further in outcome trials. Type 1 diabetesOverweight and obesityInsulin resistanceAdjunctive therapyMetformin Type 1 diabetes (T1D) results from an autoimmune destruction of pancreatic -cells, and the predominant pathophysiology is an almost absolute insulinopenia. Therefore, injectable insulin is the cornerstone of treatment, and advances in insulin therapy have led to an increase in life expectancy of T1D individuals. While there have been significant advances in the development of newer insulin analogs with more physiological pharmacokinetic profiles, continuous subcutaneous insulin infusion (CSII) and continuous gl Continue reading >>
Six-month Clinical Trial Reveals Addition Of Metformin Fails To Improve Glycemic Control In Adolescents Living With Type 1 Diabetes
Six-Month Clinical Trial Reveals Addition of Metformin Fails to Improve Glycemic Control in Adolescents Living with Type 1 Diabetes Showed improvements to cardiovascular risks—reduced weight, BMI, total daily insulin usage BOSTON, December 1, 2015––Six months of adjunctive metformin therapy does not improve glycemic outcomes in obese adolescents with type 1 diabetes, according to new research from T1D Exchange and funded by the JDRF. However, it may have a beneficial effect on measures of obesity, including weight and BMI. The results, published in the current issue of the Journal of the American Medical Association, are from the largest clinical trial to date examining the effect of metformin on overweight and obese adolescents with type 1 diabetes. Though the body mass composition of type 1 patients has traditionally been normal or underweight, recent data from the T1D Exchange shows that adolescents with type 1 diabetes have not escaped the global obesity epidemic. Metformin, an oral medication used primarily to treat type 2 diabetes by helping control blood sugar levels and improving insulin resistance, has shown significant potential benefits among adults. However, studies of adolescents have been small, of short duration, produced inconclusive results or did not focus on overweight and obese adolescents. Thus, the researchers sought to assess the efficacy and safety of metformin as an adjunct therapy in overweight adolescents with type 1 diabetes. They studied changes in HbA1c levels—a fundamental measure of diabetes management—as a primary outcome. They also explored changes in total daily insulin and fluctuations in blinded continuous glucose monitors, BMI/body composition, blood pressure, and lipids. “Being overweight or obese with type 1 diabetes h Continue reading >>
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Metformin In Type 1 Diabetes
Is this a good or bad idea? The article by Meyer et al. (1) revives a debate regarding the appropriateness of metformin use for people with type 1 diabetes. Given the potential for coexisting lactic acidosis and diabetic ketoacidosis, how can one justify its use? Indeed, there was little reason to expect a benefit in patients who were studied: nonobese type 1 diabetic subjects with HbA1c <9.0% who were taking ∼0.7 units · kg insulin−1 · day−1. A modest average reduction of daily insulin requirements, 4.3 units, as compared with an increase of 1.7 units for placebo, does not seem to be worth the trade-off of increased risk for severe hypoglycemia (19 events in metformin group vs. 8 events in placebo group). There was no differential effect in terms of HbA1c. Only 7 of 31 patients (23%) treated with metformin responded in terms of a significant (20%) reduction in insulin requirement. Furthermore, it is likely that the incidence of hypoglycemia would be much greater if more aggressive metabolic targets of HbA1c had been applied. Despite the failure to observe diabetic ketoacidosis, the limited number and short period of observation does not permit the conclusion that metformin is safe in ketosis-prone diabetic subjects. We have seen a number of type 1 diabetic patients who have received metformin prescriptions by other practitioners. It appears that these prescriptions were given because of a failure to identify latent autoimmune diabetes in adults or because the physician believed that the potential for insulin dose reduction and lipid improvement justified a putative small risk for diabetic ketoacidosis and lactic acidosis. The temptation to prescribe metformin is increased because of the high prevalence of metabolic syndrome among U.S. adults (2). Indeed, the di Continue reading >>
#40 Metformin For Patients With Type 1 Diabetes & May 2017 Update On My T1dmanagement
#40 Metformin For Patients With Type 1 Diabetes & May 2017 Update on My T1DManagement I would expect that the majority of those with diabetes, including type 1 diabetes (T1DM), have at least heard of the medication, metformin. It is primarily used to lower blood glucose (BG) in those with type 2 diabetes (T2DM), but does so by addressing insulin resistance, the primary defect in T2DM. However in recent years, it has been used off-label for persons with insulin resistance that leads to other conditions including pre-diabetes, severe obesity, polycystic ovarian syndrome (PCOS), cancer, and T1DM. Its use in T1DM has been targeted to those with signs of insulin resistance which include hypertension, elevated serum triglycerides (>150 mg/dl), reduced HDL-C (<40 mg/dl in males or <50 mg/dl in females), overweight/obesity or elevated waist-to-height ratio (>0.5) (which includes about 25% of those with T1DM). Although any of these signs can be associated with insulin resistance, the more signs one has, the higher the risk of having insulin resistance. The term double diabetes has been used to describe those with T1DM who are also insulin resistant. Insulin resistance as has been reviewed in detail in my blog post #22 primarily in the context of prediabetes and type 2 diabetes. But you may ask, How does a person with T1DM become insulin resistant? You probably wont hear very many provide an explanation for it, but here is mine. I think it is a combination of a diet high in refined (processed) carbohydrates and sugar with the use of exogenous insulin to cover those carbohydrates. Exogenous insulin is far from physiologic and there are many hours of the day or night where there is insufficient insulin to suppress hepatic (liver) glucose production leading to elevated BG (glucotox Continue reading >>
The Effects Of Metformin In Type 1 Diabetes Mellitus
The effects of metformin in type 1 diabetes mellitus 1Department of Endocrinology and Metabolism, Eskisehir State Hospital, Eskisehir, Turkey 2Department of Medical Biology, Baskent University, Ankara, Turkey 1Department of Endocrinology and Metabolism, Eskisehir State Hospital, Eskisehir, Turkey 2Department of Medical Biology, Baskent University, Ankara, Turkey 3Department of Endocrinology and Metabolism, Ankara Diskapi Teaching and Research Hospital, Ankara, Turkey 4Department of Endocrinology and Metabolism, Kilis State Hospital, Kilis, Turkey 5Department of Endocrinology and Metabolism, Duzce Ataturk State Hospital, Duzce, Turkey Selvihan Beysel, Phone: +90 553 7465802, Email: [email protected] . Received 2017 Mar 16; Accepted 2017 Dec 10. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated. This retrospective study investigated the effect of adding metformin to pharmacologic insulin dosing in type 1 diabetics on insulin therapy 1year after treatment compared with patients on insulin therapy alone. Twenty-nine adults with type 1 diabetes who had metformin added to their insulin therapy for 12months were compared with 29 adults with type 1 diabetes who remained on insulin-alone therapy. Fifty-eight patients with C peptide negative-type 1 diabetics (26 females, mean age: 29.01 7.03years, BMI: 24.18 3.16kg/m2) were analyzed. A Continue reading >>
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Adjuvant Metformin In Type 1 Diabetes
Adjunctive metformin may have small short-term benefits, but it provides no added benefit during 10-year follow-up, according to a study published online in Diabetes, Obesity and Metabolism.1 The study is the first retrospective, long-term analysis of metformin as adjuvant therapy to insulin in type 1 diabetes mellitus (T1DM). We conclude that metformin is not associated with long-term beneficial effects on BMI, HbA1c or daily insulin dose when added as adjunct therapy to intensive insulin therapy in T1DM patients, wrote lead author Chantal Mathieu, MD, PhD, of the Laboratory for Clinical and Experimental Endocrinology, KU Leuven, Belgium, and colleagues. Adjuvant metformin is often used off-label in T1DM, owing to its mechanism of action, which may improve glycemic control and decrease insulin dose, weight, and risk of hypoglycemia. While several short-term studies have supported the beneficial effect of adjuvant metformin in T1DM, whether these effects are sustained long term has remained unknown. To evaluate the long-term effects of adjuvant metformin in a real-world setting, researchers used electronic medical records of patients with T1DM seen at University Hospitals Gasthuisberg, Leuven between September 2000 and December 2014. They separated patients into two groups: those who received adjuvant metformin for 6 months or longer (metformin group, n=186) and those who refused metformin or took it for less than 6 months (control group, n=62). They also compared these groups to a baseline reference group of patients with T1DM who were never offered adjuvant metformin (n=961). Hemoglobin A1c (HbA1c), body mass index (BMI), and daily insulin dose were recorded yearly. At baseline, the metformin group had higher BMI and lower insulin doses than the control group. Both g Continue reading >>
Metformin Type 1 Diabetes
Inexpensive drug could slow heart disease for Type 1 diabetic patients Scientists at Newcastle University believe a drug commonly prescribed for Type 2 diabetes could be routinely taken by Type 1 diabetic patients to slow the development or delay heart disease. Metformin is an inexpensive treatment that is often used for Type 2 diabetes to lower blood sugar levels by reducing glucose production in the liver. The drug is not regularly given to patients with Type 1 diabetes. However, for the first time, a clinical trial has revealed metformin can promote a patient's ability to repair their own damaged blood vessels by increasing vascular stem cells. Our research is an exciting step forward as it may have positive clinical implications for patients with increased risk of cardiovascular disease by improving their treatment options Heart disease is the leading cause of illness in diabetic patients, accounting for more than half of all fatalities. Metformin may be used to lower Type 1 diabetic patients risk of developing this complication. Findings of the clinical trial are published today in the journal, Cardiovascular Diabetology . This follows previous laboratory work at Newcastle University which explored the mechanism behind metformin. Dr Jolanta Weaver , Senior Lecturer in Diabetes Medicine at Newcastle University and Honorary Consultant Diabetologist at Queen Elizabeth Hospital, Gateshead, led both studies. She believes this new research is a major development in understanding the best ways to further improve treatment in Type 1 diabetes. Dr Weaver said: As the outcomes of heart disease is worse in diabetic versus non-diabetic patients, there is a need to identify additional treatment options. Metformin could routinely be used by patients with Type 1 diabetes to help Continue reading >>
Metformin And Type 1 Diabetes – An Experiment
Metformin is not usually prescribed for Type 1 diabetes, but over the past couple years, inspired in part by Mike’s experience on it (see here, here, here and here), I’ve become interested in trying it. Not only has it been in widespread use as a treatment for Type 2 diabetes since its approval in 1994, but it’s currently being investigated for potential cognitive and anti-cancer benefits as well. As Mike has asked, “Could metformin be the new aspirin?” The typical explanation for why metformin is not prescribed to people with Type 1 diabetes is that metformin increases your insulin sensitivity — and given that, by definition, people with Type 1 don’t make any insulin, it won’t help them. But I see two obvious holes in that logic. First, people with Type 1 diabetes do have insulin in their bodies; it’s just administered in a different way (i.e. injected subcutaneously, rather than secreted by the pancreas). And as anyone who’s struggled with the dawn phenomenon knows, people with Type 1 diabetes experience insulin resistance, too. And second, metformin does more than just affect insulin sensitivity. It also appears to regulate the genes responsible for causing the liver to release glucose into your blood. As you may know, your pancreas and your liver work closely together to maintain a proper level of glucose in the blood. When you’ve got a lot of glucose in your blood, your pancreas secretes insulin to remove it (provided you don’t have Type 1 diabetes!). And when you don’t have sufficient external glucose – like when you’re sleeping — your liver releases some stored glucose so that your blood sugar does not drop too low. To put this a different way, insulin is what keeps a non-diabetic person’s blood glucose from getting too high; the Continue reading >>
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The Addition Of Metformin In Type 1 Diabetes Improves Insulin Sensitivity,diabetic Control, Body Composition And Patient Well-being.
1. Diabetes Obes Metab. 2007 Jan;9(1):143-5. The addition of metformin in type 1 diabetes improves insulin sensitivity,diabetic control, body composition and patient well-being. AIM: As many overweight people with T1DM are insulin resistant, adjuvant therapy with insulin sensitising agents, such as metformin, may be beneficial. This studyevaluated the effect of adjuvant metformin in T1DM on insulin sensitivity,diabetic control, body composition, quality of life (QOL) and treatmentsatisfaction.MATERIALS AND METHODS: A 3-month prospective open-labelled pilot study of 16patients aged 18-40 with T1DM and body mass index (BMI) >25 kg/m(2) wasperformed. The patients received 500-850 mg metformin twice daily. Insulinsensitivity, assessed by a frequently sampled intravenous glucose tolerance test [n=5], body composition, HbA(1c) and quality of life (QOL) were measured beforeand after treatment. A retrospective review of 30 patients with T1DM treated withmetformin for at least 4 months was also performed. BMI, HbA(1c) and insulinrequirements during metformin treatment was compared to pre-metformin data, andto patients treated with insulin only.RESULTS: In the pilot study, insulin sensitivity increased significantly from0.86 +/- 0.33 x 10(-4)/min/(microU/ml) to 1.17 +/- 0.48 x 10(-4)/min/(microU/ml) after 3 months adjuvant therapy (p = 0.043). This was associated with a decreasedinsulin requirement and mean daily blood glucose. There were no significantchanges in HbA(1c) or body composition. QOL significantly improved (p < 0.002).The retrospective review revealed an initial reduction in HbA(1c) (0.8 +/- 1.4%, p = 0.001). This effect diminished with prolonged treatment. BMI decreased inpatients remaining on metformin for a 2-year period (0.5 +/- 0.5kg/m(2), p =0.042).CONCLUSION: Continue reading >>
The Use Of Metformin In Type 1 Diabetes: A Systematic Review Of Efficacy
The use of metformin in type 1 diabetes: a systematic review S. Vella &L. Buetow &P. Royle &S. Livingstone & Received: 8 September 2009 / Accepted: 19 November 2009 Aims/hypothesis As adding metformin to insulin therapy has been advocated in type 1 diabetes, we conducted a systematic review of published clinical trials and clinical trial databases to assess the effects on HbA insulin-dose requirement and adverse effects. Methods We constructed evidence tables and fitted a fixed- effects model (inverse variance method) in order to assess heterogeneity between studies and give a crude measure of Results Of 197 studies identified, nine involved random- isation with informed consent of patients with type 1 diabetes to metformin (vs placebo or comparator) in either a parallel or crossover design for at least 1 week. We noted marked heterogeneity in study design, drug dose, age of participants and length of follow-up. Metformin was associated with reductions in: (1) insulin-dose requirement (5.710.1 U/day in studies); (3) weight (1.76.0 kg in three of six studies); and (4) total cholesterol (0.30.41 mmol/l in three of seven studies). Metformin was well tolerated, albeit with a trend towards increased hypoglycaemia. Formal estimates of combined effects from the five trials which reported appropriate data indicated a significant reduction in insulin dose (6.6 U/day, p<0.001) but no significant reduction in (absolute reduction 0.11%, p=0.42). No reported requirement in type 1 diabetes but it is unclear whether this is sustained beyond 1 year and whether there are benefits for cardiovascular and other key clinical outcomes. Tight glycaemic control using intensive insulin therapy was shown in the DCCT to reduce rates of microvascular complications in type 1 diabetes [1]. However, Continue reading >>
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A New Perspective On Metformin Therapy In Type 1 Diabetes
Home / Conditions / Type 1 Diabetes / A New Perspective On Metformin Therapy In Type 1 Diabetes A New Perspective On Metformin Therapy In Type 1 Diabetes The evolution of metformin therapy through the decades. Studies such as the Diabetes Control and Complications Trial (DCCT) and its Epidemiology of Diabetes Interventions and Complications (EDIC) post-randomization follow-up have established that the risk of cardiovascular and microvascular complications in patients with type 1 diabetes can be mitigated with stringent glucose control. However, maintaining blood glucose levels within goal range remains difficult for patients to achieve. The DCCT demonstrated that as HbA1c goals are approached the incidence of hypoglycemia increases exponentially. The risk and fear associated with hypoglycemia is a key factor in patient’s and practitioner’s difficulties in reaching target blood glucose levels. As such, healthcare providers err on the side of caution when setting goals for their patients. Another issue facing patients with type 1 diabetes is the prevalence of insulin-induced weight gain and eventual insulin resistance and subsequent insulin dose requirement increases. Patients often experience increased blood pressure and LDL-cholesterol levels as consequence. Because of these challenges non-insulin therapies have emerged as possible solutions for patients with type 1 diabetes. Following the UK Prospective Diabetes Study (UKPDS) published in 1998 the world was introduced to metformin hydrochloride as a safe option for all type 2 diabetes patients and was no longer reserved only for obese patients. The UKPDS demonstrated that obese patients with type 2 diabetes gained less weight compared to other oral medication options, had less incidence of hypoglycemic events and Continue reading >>
Metformin For Type 1 Diabetes - Really? Why?
You've heard it before: someone with type 2 diabetes goes on insulin. That's no surprise. But how often have you heard the reverse — someone with type 1 going on Metformin? Since the launch of Symlin in 2005, it's not uncommon for people to treat their type 1 diabetes with a supplemental injectable medication. But hang around long enough, and you too might get to know someone with type 1 who takes insulin and oral meds, those formerly known as "type 2 only" drugs. Really? Type 1's taking oral meds alongside insulin? To clarify this, I just had to query some experts. Just like in type 2 diabetes, people with type 1 diabetes can sometimes suffer from insulin resistance (when the insulin that's present can't perform it's work properly), and Metformin can lower your insulin requirements by helping the body make better use of the stuff — in this case coming from an injection or insulin pump. Gary Scheiner, CDE, author, and head of Integrated Diabetes Services in Wynnewood, PA, explained it this way: "Some of the more creative and aggressive endos are prescribing Metformin for type 1's, particularly if they are overweight or requiring very large basal insulin doses. In addition to having some mild appetite-suppression effects, it will enhance insulin sensitivity by hepatic cells (in the liver) and limit the amount of glucose secreted by the liver. Personally, I think it can be helpful during adolescence as well. As long as the patient has good liver and kidney function, the side effects and risks are negligible." I also learned this: a couple of other uses of Metformin for women to consider are PCOS (ovary disease) and pregnancy. Kelley Champ Crumpler, RN, who is a diabetes nurse educator and a type 1 diabetic married to an endocrinologist with type 1 diabetes (how's that Continue reading >>
Effect Of Metformin In Patients With Type-1 Diabetes With Inadequate Glycaemic Control By Insulin And Diet
Ninety percent of patients with type-1-diabetes will develop late-diabetic complications in the eyes, kidneys, nervous- or cardiovascular-system. Poor glycaemic control is an important risk-factor for development of these late-diabetic complications. The Diabetes Control and Complications Trial (DCCT)-study showed, that improved glycaemic control can prevent the development and progression of these late-diabetic complications. Until now treatment with insulin- and diet-therapy has been the only treatment-modalities available to improve the glycaemic control in patients with type-1-diabetes. A substantial number of these patients still have long-standing poor glycaemic control despite intensive treatment with insulin- and diet-therapy. The antidiabetic drug metformin has shown to be able to improve the glycaemic control in combination with insulin and furthermore reduce both mortality and the risk of developing cardiovascular disease in patients with type-2-diabetes. Only few small studies have investigated the effect of treatment with metformin in patients with type-1-diabetes. These studies have suggested a positive effect of metformin in these patients too. Method: 100 patients with type-1-diabetes with persistent poor glycaemic control i.e. HbA1c > 8.5% during the last 12 months are eligible. Patients are treated for one month with placebo. Hereafter half of the patients will be treated with metformin and the other half continues with placebo for 12 months both as add-on therapy. All patients are continuing ongoing treatment with insulin throughout the study. Before and after the start of treatment with metformin the effect on glycaemic control and other known risk-factors for development of cardiovascular disease i. e. blood-pressure, fasting lipids, urine-albumine- Continue reading >>
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Metformin In Type 1 Patients Slows Development Of Heart Disease
Scientists believe drug commonly prescribed for T2 could be routinely taken by T1 patients. Metformin is an inexpensive treatment that is often used for type 2 diabetes to lower blood glucose levels by reducing glucose production in the liver. Normally the drug is not regularly given to patients with type 1 diabetes. However, for the first time, a clinical trial has revealed metformin can increase vascular stem cells, which can promote a patient’s ability to repair their own damaged blood vessels. Metformin may be used to lower risk of developing heart disease in patients who have type 2 diabetes, which is the leading cause of illness in type 1 diabetes, accounting for more than half of all fatalities. Dr. Jolanta Weaver, Senior Lecturer in Diabetes Medicine at Newcastle, led two of the studies and believes this new research is a major development in understanding the best ways to further improve treatment in type 1 diabetes. She added that, “As the outcomes of heart disease is worse in diabetic versus nondiabetes patients, there is a need to identify additional treatment options. Metformin could routinely be used by patients with type 1 diabetes to help lower their chances of developing heart disease, by increasing a repair mechanism created by vascular stem cells released from the bone marrow. For the first time, this study has shown metformin has additional benefit beyond improving diabetes control when given to patients with relatively well controlled type 1 diabetes. We have established the drug increases patient’s own vascular stem cells, which will help delay or slowdown heart disease. Our research is an exciting step forward as it may have positive clinical implications for patients with increased risk of cardiovascular disease by improving their treatment Continue reading >>
Is Metformin Effective For Type 1 Diabetes?
Is Metformin Effective for Type 1 Diabetes? At what point, if any, should one consider the addition of metformin to the regimen of an adherent patient with type 1 diabetes who is not well controlled on insulin? Associate Professor, Department of Pharmacy Practice, Presbyterian College School of Pharmacy; Clinical Pharmacy Specialist, Good Shepherd Free Medical Clinic, Clinton, South Carolina The addition of off-label metformin to insulin therapy to improve insulin sensitivity, promote weight control, and reduce insulin dose requirements in patients with type 1 diabetes has been assessed in systematic reviews.[ 1 , 2 ] One review sought to assess the effects of metformin when added to insulin therapy for type 1 diabetes in adolescents.[ 1 ] The Cochrane Library, MEDLINE, and EMBASE were searched, along with databases of ongoing clinical trials, for randomized controlled trials of at least 3 months' duration. Trials that were included compared metformin added to insulin vs insulin therapy alone. Two trials met inclusion criteria, representing 60 patients in total. Although a lack of heterogeneity made meta-analysis impossible, the authors did note that both studies found a reduction in glycosylated hemoglobin A1c values when metformin was added to insulin. One of the studies also showed a 10% decrease in insulin dosage among those taking metformin. Hypoglycemia and gastrointestinal disturbances were among the most commonly occurring adverse effects of combination therapy. Another systematic review evaluated the addition of metformin to insulin in type 1 diabetes.[ 2 ] This review identified 9 studies, including both adolescents and adults, that involved randomization with informed consent. The studies compared metformin vs placebo or another comparator in parallel or cro Continue reading >>
