Perception of failure and its impact on fostering positive change

We all have those patients who seem to understand all of the education provided, recognize the risks of elevated blood sugars, verbalize that this time they will make that one jointly decided upon change, and yet, time after time, they return without making any progress. A recent editorial that I read in JAMA helped me to better understand why these patients may be struggling. (1) I think that many of my patients feel like they have failed when they see elevated A1cs, blood sugar numbers out of range or weight gain. It may be the response to perceived failure that is impeding these patients from achieving their goals.

According to the editorial, people respond to failure on an emotional level and on a cognitive level.(1) In other words, individuals experience feelings about the failure, but also conduct an internal assessment of the cause the failure. Patients who decide that the failure is due to an uncontrollable cause and feel shame are less likely to make changes. Low self-esteem often leads patients along this pathway and patients develop avoidant behaviors to escape these negative feelings.(2)

How can we help?

There are many articles from those in business about how to help someone reset their perception of failure. After all, there are all of those quotes circulating on social media about how founders of companies had hundreds of failures before making their millions. They know about overcoming failure. In a TEDX talk, business person Fred Colantonio talks about how he has learned through his life experiences that failure needs to be reframed as a part of life. (3) Failure is not an absolute. It is a stepping stone and an opportunity to learn and grow.

What this means to me is that these patients can be helped by focusing on the positive instead of the negative. If we can help them see what they have already accomplished instead of what still needs to be fixed this may prevent those feelings of shame that are getting in the way. Also, reframing a perceived failure as just another bump along the road of life that they are capable of impacting may also help. Finally, cheering them on for every small step can help their self-esteem and may help to cement this desired shift in attitude.

S. Mimi Mukherjee, PharmD, CDE, BCPS

1. Kangovi S, Asch DA. Behavioral phenotyping in health promotion. JAMA. 2018;319(20):2075-2076.
2. Webb TL. Chang B. Benn Y. “The ostrich problem”:motivated avoidance or rejection of information about goal progress. Soc Personal Psychol Compass. 2013;7(11):794-807.
3. Colantonio, F. How perception of failure affects success. Published Jun. 24, 2014. Accessed Jun. 8, 2018.


What in the World?! Meaningful Outcome Measures Beyond HbA1c in Type 1 Diabetes

By a rhetorical raise of hands, how many of us utilize glycated hemoglobin (HbA1c), along with self-monitoring of blood glucose (SMBG), to guide clinical decision-making in the pursuit of glycemic control in our patients with diabetes mellitus (DM)? I would venture to assume that 100% of us would raise our hand as we are devotees of clinical practice guidelines. Second question of the day: how many children and adults with type 1 diabetes mellitus (T1DM) achieve glycemic targets? The correct answer, despite the use of HbA1c and multiple daily SMBGs, only 20% of children and 33% of adults with T1DM achieve HbA1c-driven glycemic targets. Growing evidence of adverse outcomes due to hypoglycemia and suggestion of chronic DM complications as a result of not only sustained hyperglycemia but glycemic variability endorse opportunities for re-defining how we assess efficacy and safety of therapies while in pursuit of glycemic control.1,2  This opportunity requires consideration of the patient’s quality of life, understanding of the dynamic nature of glucose, and the prevention of life-threatening complications due to poor glycemic control.1,2 A Steering Committee – comprised of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine and the T1D Exchange – sought to do just that in expressing that the time is now to optimize utility of new devices that make it feasible to assess the efficacy and safety of antihyperglycemic therapies and technologies beyond HbA1c.1

The described Steering Committee has published a joint consensus statement with the objective to identify and define clinically meaningful outcome measures for patients with T1DM beyond HbA1c.1 As I’m sure we are all well aware, periodic evaluation of HbA1c, as supported by professionally recognized treatment guidelines, is an established surrogate measure in assessing the efficacy and safety of antihyperglycemic therapies and technologies in our T1DM patients.3,4 However, HbA1c is not without its’ shortcomings. The surrogate measure has an inability to capture short-term variations in blood glucose, reflect  the influence of variations in glycosylation, and the impact of variations of glycemic control on patients’ quality of life and incidence of acute events of hypo- and hyperglycemia.1,5  The Steering Committee elaborates that with the technological advances, particularly growing utilization and reliability of CGMs, the stage is primed to pursue utilization of other clinically meaningful outcome measures in clinical practice, research and development of therapies in T1DM.1

The Steering Committee identified the following outcome measure to define – hypoglycemia, hyperglycemia, time in range, diabetic ketoacidosis (DKA), and patient-reported outcomes (PROs). By standardizing the definitions of the listed outcome measures, the committee’s immediate goal is for their use as primary and secondary endpoints in clinical research. This inclusion aims to achieve comprehensive evaluation and understanding of the impact new therapies and technologies have on influencing management of T1DM. Additionally, the utility of these outcome measures in clinical practice are set to empower the clinician to better derive individualized treatment plans for our T1DM patients.

Based on expert opinion and published evidence, the Steering Committee has constructed the following definitions that are clinically meaningful, applicable to nonpregnant patients with T1DM, measurable using existing technologies and applicable regardless of time of day:1

Level 1 Measurable glucose concentration < 70 mg/dL but ³ 54 mg/dL
Level 2 Glucose < 54 mg/dL
Level 3 Severe event characterized by altered mental and/or physical status requiring assistance
Level 1 Elevated glucose – glucose > 180 mg/dL and glucose £ 250 mg/dL
Level 2 Very elevated glucose – glucose > 250 mg/dL
Time in Range:
·    Percentage of readings in the range of 70 – 180 mg/dL per unit of time
·    Elevated serum or urine ketones (greater than ULN) and serum bicarbonate < 15 mmol/L or blood pH < 7.3
·    Report of the status of a patient’s health condition, health behavior, or experience with healthcare that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else.

*as defined by the Food and Drug Administration (FDA) and endorsed by the defined Steering Committee

Although the Steering Committee does not intend for these clinically meaningful outcome measures to replace HbA1c, there is opportunity for these outcomes to augment the limitations of HbA1c. Notably, the standardized definitions of hypoglycemia, hyperglycemia and DKA are coordinated with a previous publication regarding use of CGMs. The advancement and availability of CGM devices are the likely key ingredient to filling the gaps in use of HbA1c alone, as they function to build the bridge to being able to comprehensively capture the efficacy and safety of technologies and antihyperglycemic therapy in clinical research, development and practice.1,6 However, we certainly require a growing body of research to identify the long-term clinical, economic and humanistic impacts directed by the standardization of these clinically meaningful outcome measures. In addition to standardization, it will be of mounting importance for these clinically meaningful outcome measures to be presented in a consistent format and as broadly available to clinicians as HbA1c. While we anticipate more evidence, how do you see your evaluation and management of patients with T1DM being impacted by the standardization and availability of these clinically meaningful outcome measures?


  1. Agiostratidou G, Anhalt H, Ball D, et al. Standardizing clinically meaningful outcome measures beyond HbA1cfor type 1 diabetes: a consensus report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange. Diabetes Care. 2017; 40(12):1622-30.
  2. Wright L and Hirsch IR. Metrics beyond hemoglobin A1c in diabetes management: time in range, hypoglycemia, and other parameters. Diabetes Technol Ther. 2017;19(Suppl 2):S16-26.
  3. American Association of Clinical Endocrinologists. Treatment of type 1 diabetes. (accessed 2018 May 1).
  4. American Diabetes Association. Glycemic targets: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(Suppl 1):S55-64.
  5. Argento NB, Nakamura K, Sala RD, et al. Hemoglobin A1c, mean glucose, and persistence of glycation ratios in insulin-treated diabetes. Endocr Pract. 2014;20(3):252-60.
  6. Danne T, Nimri R, Battelino T, et al. International consensus on use of continuous glucose monitoring. Diabetes Care. 2017;40(12):1631-40.

Cashing Out on the Sugar Checks?

I know I am not the only one who struggles to get patients with diabetes to check their blood sugars consistently.  As a clinician, studies have revealed to us that self-monitoring of blood glucose (SMBG) reduces Hemoglobin A1c (HbA1c) and improves patients’ blood sugars1,2; however, a recent study revealed that it may no longer be necessary, particularly if the patient is not using insulin.

HbA1c is a standard measurement of glycemic control that is readily available to health care providers for managing diabetes and allows us to confirm home blood sugar readings to ensure proper control.  Historically, we have focused on a target HbA1c of less than 7% in patients with diabetes, while suggesting more lenient goals (< 8%) for patients with complicated cardiovascular disease, short life expectancy, multiple uncontrolled co-morbid disease states, or those at high risk for hypoglycemia. The American College of Physicians (ACP) released new guidelines in March 2018 regarding goals of therapy for patients with diabetes.  ACP suggested clinicians should target HbA1c levels between 7 – 8 percent, rather than 6.5 – 7 percent for patients with diabetes.3  Much controversy exists with this recently released statement from ACP as the American Diabetes Association (ADA) reported that these recommendations were not primarily based upon compelling evidence in trials like ACCORD, ADVANCE, VADT, and UKPDS.  ADA discussed how these trials shaped their recommendations for tighter control, demonstrating decreased microvascular complications and suggested clinicians continue to utilize more stringent goals for most patients with diabetes.4  In addition to the ADA, the American Association of Clinical Endocrinologists (AACE), the American Association for Diabetes Educators (AADE), and the Endocrine Society all strongly disagreed with ACP’s recommendations as well.  So tell me, where do YOU stand on the ACP guideline recommendations for HbA1c??

Part of this control requires patient involvement at home.  In a recent study “Glucose Self-monitoring in Non–Insulin-Treated Patients with Type 2 Diabetes in Primary Care Settings:  A Randomized Trial”, HbA1c was found to be no different in the patients who were checking their blood sugars versus the patients who were not.  Briefly, 450 patients with diabetes (median time of having the disease was 6 years) were randomized to one of three groups:  No Self-Monitoring of Blood Glucose (SMBG), once-daily SMBG, and once-daily SMBG with enhanced patient feedback including automatic tailored messaged delivered via the glucometer.  The outcomes measured were HbA1c levels and health-related quality of life (HRQOL) at 52 weeks.  No significant differences were found in either endpoint, demonstrating that glucose monitoring does not necessarily improve HbA1c, nor did it affect quality of life in this population.5

This study made me think about my own patient population and how I might apply the results.  Some of my patients do a fantastic job monitoring their blood sugars, writing them down, and bringing them to their visits for evaluation—this, of course, makes my job easier.  Other patients struggle to check their blood sugars and rarely do it, often reporting the burden of pricking their fingers and the pain associated with using the lancing device.  This study provided practical application to the latter group and is a patient-centered focused study, which is critical given healthcare’s emphasis on patient-centered care outcomes in recent years.  The evidence allows us to see that some patients may be just fine without checking their sugars regularly but more information is still needed in patients who are insulin dependent. Involving patients in these decisions is crucial because it provides them with a sense of responsibility about their health and wellness but also aids in our ability to see what is going on at home to make better patient-centered clinical decisions.

As an ambulatory care pharmacist who heavily focuses on diabetes management, this study makes me question the need for SMBG for improving outcomes.  When the benefits are lacking, what really is the point?  Checking blood sugars daily can be burdensome, costly, and as shown above, may not improve outcomes. To clarify, I am not suggesting that your patients do not need to be monitoring their blood sugars.  In fact, I still think there are great benefits of SMBG, especially in a new diabetic who is motivated to make lifestyle changes, but that population wasn’t studied in Young et al., and so more research still needs to be completed.  I do see a potential benefit to recommend less SMBG for lowering patient costs if there is no change in HbA1c and HRQOL.  Many of my patients struggle to afford test strips, particularly those who do not have proper coverage.  Additionally, many of my patients are on a strict budget and have trouble affording food, not to mention “healthy food” that will better control their blood sugars.  Based on this information, I am suggesting that patients be part of the plan, and that as health care providers, we discuss the needs of our patients, the goals of therapy, and design a plan that is specific to each individual we are treating.  More evidence is still needed, but less SMBG is certainly something I have introduced to my practice and will continue to work with my patients individually to set realistic expectations about their diabetes control.

Personally, I believe SMBG is appropriate in some circumstances but may not be helpful in others.  Each individual patient requires a different goal and we should be utilizing guidelines for what they actually are:  “Guidelines”.  Diabetes is a very individualized disease state that often leads to many other conditions, and proper control along with different medication therapies have demonstrated positive outcomes related to both micro- and macro-vascular complications.  So my question to you as a practicing clinician:  Do YOU see any value in SMBG?  If so, how do YOU use it in your diabetic non-insulin dependent patient population?

Written by:  Nicole Slater, PharmD, BCACP


  1. Polonsky WH, Fisher L, Schikman CH, et al. Structured self-monitoring of blood glucose significantly reduces A1C levels in poorly controlled, noninsulin-treated type 2 diabetes: results from the Structured Testing Program study. Diabetes Care 2011;34:262–267
  2. Schwedes U, Siebolds M, Mertes G, et al. Meal-Related Structured Self-Monitoring of Blood Glucose:  Effect on diabetes control in non-insulin treated type 2 diabetic patients.  Diabetes Care 25:1928-1932.
  3. Qaseem A, Wilt TJ, Kansagara D, et al. Hemoglobin A1c Targets for Glycemic Control with Pharmacologic Therapy for Nonpregnant Adults with Type 2 Diabetes Mellitus:  A Guidance Statement Update from the American College of Physicians.  Ann Intern Med 2018.  Available from:  Accessed 5 April 2018.
  4. Glycemic Targets:  Standards of Medical Care in Diabetes-2018.  American Diabetes Association.  Diabetes Care 2018;41(Supplement 1):S55-S64.  Available from:  Accessed 4 April 2018.
  5. Young LA, Buse JB, Weaver MA. Glucose Self-monitoring in Non–Insulin-Treated Patients With Type 2 Diabetes in Primary Care Settings:  A Randomized Trial.  JAMA 2017;177(7):920-929.


SGLT-2 Inhibitors for Type 1 Diabetes: A Worthwhile Gamble?

SGLT-2 inhibitors continue to be studied in type 1 diabetes despite the FDA warning about euglycemic diabetic ketoacidosis (DKA) and knowing that patients with type 1 diabetes are at increased risk of DKA compared to their type 2 counterparts. 1 Perhaps, it’s because of the blood pressure lowering, weight loss, and positive cardiovascular outcomes observed in type 2 diabetes. It sure would be exciting if these drugs could be viable options for patients with type 1 diabetes.

So, what does the literature say? The DEPICT-12 trial was a double-blind, randomized, parallel-controlled, study that included patients with uncontrolled type 1 diabetes. Patients were randomly assigned to dapagliflozin 5 mg or 10 mg once daily or placebo. The primary outcome was change in A1C after 24 weeks. In total, 833 patients were included: mean baseline A1C=8.53%, mean BMI=28kg/m2. At week 24, both doses of dapagliflozin significantly reduced A1C compared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0.42% [95% CI −0.56 to −0.28; p<0.0001] and for dapagliflozin 10 mg vs placebo was −0.45% [−0.58 to −0.31; p<0.0001]). Rates of hypoglycemia and DKA were similar between groups. The authors concluded that dapagliflozin is a promising adjunct treatment to insulin to improve glycemic control in patients with inadequately controlled type 1 diabetes. It’s important to note that the study design limited insulin reduction to 20% based on previous studies to limit DKA events.3 It seemed to work in this case!


The newest SGLT2 inhibitor to be explored is sotagliflozin which is actually a dual SGLT1 and SGLT2 inhibitor. SGLT1 has additional effects on the proximal intestine and by inhibiting SGLT1, there is reduced glucose absorption which improves postprandial hyperglycemia. In a phase III, double-blind, randomized, controlled trial (InTandem3)4, 1402 patients with type 1 diabetes were randomized to sotagliflozin 400mg/day or placebo for 24 weeks. Baseline characteristics include mean BMI of 28kg/m2 and 71% of patients with BMI≥25 kg/m2. Mean insulin doses were 56-58 units/day and mean A1C was 8.2%. Significantly more patients in the sotagliflozin group compared to placebo achieved A1C lower than 7% (207 patients [29.6%] vs. 111 [15.8%]). The A1C reduction from baseline to week 24 was significantly greater in the sotagliflozin group (difference, −0.46%; P<0.001). There was also greater weight loss with sotagliflozin (difference=−2.98 kg; P<0.001). In the sotagliflozin group, the placebo-corrected reductions from baseline in the mean daily total, bolus, and basal doses of insulin were −5.3 units per day (−9.7%), −2.8 units per day (−12.3%), and −2.6 units per day (−9.9%), respectively (P <0.001 for all comparisons). Overall, rates of hypoglycemia were similar between groups. Diarrhea (4.1% vs 2.3%) and genital mycotic infections (6.4% vs 2.1%) were more common with sotagliflozin compared with placebo, respectively.  The rate of acidosis-related adverse events was 8.6% in the sotagliflozin group and 2.4% in the placebo group with actual DKA occurring in 3.0% in the placebo group and 0.6% in the placebo and more cases in those on insulin pumps.

The clinical efficacy is quite remarkable, but the increase risk of DKA is concerning, especially because the trial included a higher level of education and monitoring for DKA than what occurs in most usual clinical practice. Sotagliflozin is also most similar structurally to canagliflozin, and although bone loss and amputations have not been seen with sotagliflozin, we lack long term outcomes.5

A meta-analysis by Chen and colleagues6, reviewed over 11 trials and 581 patients, assessed the safety and efficacy of SGLT2 inhibitors vs. placebo in those with T1DM who were on insulin. The mean baseline characteristics included age of 41, duration of diabetes 21.28 years, A1C 8.026%, and BMI 27.25 kg/m2 . Hemoglobin A1C  was reduced by 0.37% and total body weight was reduced by 2.54kg,  Total adverse effects were similar between groups,  but not surprisingly, there was an increase in DKA in those on SGLT2 inhibitors.

Overall, SGLT-2 inhibitors show promise in type 1 diabetes for weight control and A1C lowering. Based on EMPA-REG and CANVAS, they may even have potential to improve cardiovascular outcome as seen in patients with type 2 diabetes. Perhaps, if we follow the rule in the DEPICT-1 dapagliflozin trial and limit insulin reduction to no more than 20%, we can prevent DKA from occurring?

What do you think? Is the benefit worth the risk? This is such a difficult population to achieve A1C goal, which is often plagued by hypoglycemia and unpredictable hyperglycemia and hypoglycemia. (See Adam Brown’s 42 factors that can impact BG7) . It would be nice to have another tool to treat these patients. Yet, DKA can be life threatening and is it worth the gamble even if the overall rates are low?  It reminds me a bit of Russian roulette. Is it just bound to happen if we use these agents enough?

Then again, maybe one day, insulin pump technology will advance that every patient will have an artificial pancreas. But until that day comes, it sure would be nice to have another medication to use in this difficult to treat population.


  1. FDA Drug Safety Communication. Available at: Accessed 3/18/18.
  2. Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2017;8587(17):1-13. doi:10.1016/S2213-8587(17)30308-X.
  3. Henry RR, Rosenstock J, Edelman S, et al. Exploring the potential of the SGLT2 inhibitor dapaglif lozin in type 1 diabetes: A randomized, double-blind, placebo-controlled pilot study. Diabetes Care. 2015;38(3):412-419. doi:10.2337/dc13-2955.
  4. Garg SK, Henry RR, Banks P, et al. Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes. N Engl J Med. 2017:NEJMoa1708337. doi:10.1056/NEJMoa1708337.
  5. Rendell MS. Efficacy and safety of sotagliflozin in treating diabetes type 1. Expert Opin Pharmacother. 2017;0(0):14656566.2017.1414801. doi:10.1080/14656566.2017.1414801.
  6. Chen J, Fan F, Wang JY, et al. The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: A systematic review and meta-analysis. Sci Rep. 2017;7(March):1-9. doi:10.1038/srep44128.
  7. Factors Affect BG Control. Diatribe. Available at: Accessed 3/18/18.

Written by: Diana Isaacs, PharmD, BCPS, BC-ADM, CDE, Clinical Pharmacy Specialist, Cleveland Clinic Diabetes Center

Substance Use Disorder and Diabetes

It should be of no surprise that we have a prescription drug abuse epidemic in this country.  How does that impact diabetes management and education? What about other substances?  Cigarette smoking and alcohol use are prevalent among individuals with diabetes in the US, but little is known about screening and treatment for substance use disorders in the diabetes population.

What are the clinical implications of the public health problem of coexisting substance use and diabetes? Diabetes is major cause morbidity and mortality in the US with an estimated 24 million adults in the US with type 2 diabetes.  In addition, prescription drug abuse affects nearly 3 million adults.

Approximately 20% of adults aged 18 years or older with diabetes report current cigarette smoking. The prevalence of current alcohol use in the diabetic population is estimated to be around 50%–60% in epidemiological surveys and treatment-seeking populations. Cigarette smoking is associated with an increased risk of type 2 diabetes in a dose-dependent manner and is an independent modifiable risk factor for development of type 2 diabetes. Patients with diabetes patients with an alcohol or other drug use disorder show a higher rate of adverse health outcomes including more frequent and severe health complications as well as an increased risk of hospitalization, and longer hospital stays. They are also less likely to seek routine care for diabetes or adhere to diabetes treatment than those without an alcohol or other drug use disorder.

There is an increased trend to facilitate integration of preventive services and evidence-based treatments for substance use disorders with diabetes care in community-based medical settings.  Do you know the treatment options in your community? How do you address substance abuse disorders in your patients with diabetes?

Prediabetes and diabetes prevention: Are we doing enough? What could we be doing differently?

Time and time again, as I work with prediabetes patients in clinic, I see many individuals come in feeling defeated.  At our last visit, my patient was really ready to “get serious” about watching portions, making healthy food choices, and getting in the recommended physical activity of moderate aerobic exercise for 150 minutes per week.  My patient did well for a week or two, and then life happened.  They had a sick child, work asked for some overtime, and there were multiple family gatherings that revolved around food (think holidays).  And my patient “fell off the bandwagon” so to speak.  After a couple of days of dietary indiscretion, and not making it to the gym, they thought, “to heck with it” and binged on comfort foods while watching T.V. as a method of stress reduction.  They gained a few more pounds.  Guilt crept in, and that turned into missing a follow-up appointment with me, because they were embarrassed that I would think poorly about the lack of effort.

What I described is too often a reality, and becomes a dangerous cycle for patients.  A cycle that leads to depression, which can lead to giving up the treatment plan, then worsening glycemic control, a feeling of overwhelm or lack of control, and then finally, despair—once prediabetes becomes Type 2 diabetes.

We know from the Diabetes Prevention Program (DPP) that intensive lifestyle modifications are effective, and the efforts needed don’t seem too difficult to those of us who are already doing them on a habitual basis.1 But for many with prediabetes, the modifications needed are a complete overhaul from what they are already doing.  For example, you can’t easily go from two double cheeseburgers with fries and regular soda for lunch on the run, to an expectation of eating a large plate of green leafy vegetables with a 3 oz. portion of protein and 30-45 grams of carbohydrate on the side.  It sets a person up for failure. Change takes discipline, but also, time and planning.  You start with subtracting one cheeseburger, lots of encouragement, and maybe a 10 minute walk around the block.  Add in a behavioral health session or two to rid the mind of focusing on failure, and what is not possible, and instead think about what is possible.

Diabetes Prevention Program outcomes, which included a 58% reduction in 3-year diabetes incidence and 34% reduction in 10-year diabetes incidence were achieved in the intensive lifestyle group, but not without significant efforts on the part of both participants and the clinicians and educators working with them.1,2  Lifestyle measures included a healthy, low calorie, low-fat diet (flexible, individualized, and culturally sensitive) and the 150 minutes of physical activity per week described.  Participants in this group had an incredible amount of support to achieve this:  1) A 16-lesson curriculum covering diet, exercise, and behavior modification designed to help achieve goals, 2) one-to-one meetings for 16 sessions occurring over 24 weeks, 3)subsequent individual sessions (at least every other month), AND 4) group sessions with case managers to reinforce behavioral changes.  This all occurred in the first year.  There was support that followed that as well.  Participants got frequent reminders of what they needed to do, frequent encouragement, and mild “nagging” if they didn’t show up to exercise (“we missed seeing you today, Mr. Smith”).  Don’t forget that study participants get financial compensation as well.  Could our patients do better with a free gym membership, cooking lessons, constant encouragement from prediabetes “cheerleaders” and financial rewards?  Probably!  Also, we cannot discount the concept that study participants tend to be more motivated in general than those who don’t have the time or interest in participating in a study.

Why do people still progress on to developing type 2 diabetes, despite some attempt at lifestyle measures?  There could be a strong family history of rapid progression of disease.  The ability to replicate the DPP in a real-world setting is very challenging.  Positive outcomes in the intensive lifestyle group outcomes were more commonly seen in patients with impaired glucose tolerance (IGT), so the measures may not have fully addressed impaired fasting glucose (IFG).1  Women with a history of gestational diabetes mellitus (GDM) faired equally well with metformin as with lifestyle interventions, as did patients in the largest BMI group (≥35 kg/m2).1,3, 4 There may be other pathophysiologic reasons that are not fully addressed with lifestyle measures alone.  A progressive disease, by nature, often requires add-on therapies.  We also know that when prediabetes is identified by use of A1C criteria, we are only getting part of the picture.  A1C is still not an ideal diagnostic measure, and there can be lower sensitivity when using the A1C for diagnostic purposes—especially at the lower end of the A1C range.5   A1C can be affected by a number of factors that influence hemoglobin glycation. 5 In addition, The American Diabetes Association (ADA) and American Association of Clinical Endocrinologists (AACE), often partnered with the American College of Endocrinology (ACE), are not consistent in defining diagnostic cut points for A1C as it relates to prediabetes.5,6.  Lastly, there are the individual reasons already stated previously—life gets busy!  There may be a multitude of other reasons; but we know that translation of DPP to real world settings can be less than ideal and outcomes are not always identical.  For example, a systematic review and meta-analysis which included 22 translational diabetes prevention programs showed that the mean level of weight loss was approximately one-half to one-third of the levels reported in the DPP.7

We also need to remember that Diabetes Prevention Program outcomes did include positive results for metformin—just to a lesser degree than for the intensive lifestyle group.  Metformin at a dose of 850 mg twice daily resulted in a 31% reduction in progression from prediabetes to Type 2 diabetes within the almost 3 year follow-up period, and resulted in an 18% reduction in the 10-year follow up period.1,2  The metformin group in the DPP did not receive any lifestyle intervention, but were provided with “standard” care or counseling that could be more similar to what is received in many typical primary care settings.  I often wonder, how powerful would it have been to have had a group studied with the combination of intensive lifestyle AND metformin?  Nonetheless, the data with metformin alone doesn’t look too shabby!  In the words of the simple-minded Peter Griffin, “why are we NOT funding this??”8

Lifestyle interventions were considered more cost effective than metformin in the DPP; however, metformin was not available as a generic formulation at the time.With the availability of $4 per month immediate-release metformin at many pharmacies across the nation, it almost seems like a no brainer for a prediabetes patient without contraindication.  Metformin therapy for diabetes prevention is now a grade A level recommendation in the American Diabetes Association Standards of Medicare Care for 2018; especially for those with BMI ≥35 kg/m2, those aged <60 years, and women with prior GDM—all the groups that benefitted the most in the DPP.10

For patients that cannot tolerate an inexpensive immediate-release metformin at a dose of 850 mg twice daily; generic extended release formulations are a slightly more expensive, but a reasonable alternative that often results in less GI intolerance.11-15  The least costly formulations are available as 500 mg tablets.  I start with 500 mg of the extended release daily, and titrate to at least 1500 mg daily (typically, 500 mg in the morning and 1000 mg in the evening), and increase up to 2000 mg daily, in divided doses.  For previous cases of GI intolerance, I have better luck avoiding future intolerance when I recommend that the extended release formulation be administered twice daily, instead of opting for once daily.  If adherence issues surface, once daily administration can be tried.

For patients who still cannot take metformin, there are multiple other good pharmacotherapeutic options for prediabetes, although often at a higher cost.  Most patients would not prefer to use basal insulin for diabetes prevention; however the work and theories set forth by Dr. Ralph DeFronzo and subsequent research certainly support its use, consistent with the concept of beta cell defect occurring early in disease. 16,17,18  We know from this research that there appears to be a period of glucose intolerance and pathophysiologic changes that long precede the development of diabetes.16,17  The other treatment modalities described in the table below are supported by good outcomes and share a physiologic basis for use (see the hyperlink for the actions targeted).17  Consider these alternatives to metformin in select patients, as appropriate.

Diabetes Prevention Pharmacotherapy Table 1.18.18

In summary, I would never advocate for eliminating completely lifestyle measures in prediabetes or diabetes; these should always be encouraged.  But I’m more of a realist than an idealist.  And I think that we could be more aggressive in employing all types of diabetes prevention strategies, especially pharmacotherapy, than what appears to be the current standard of practice in many clinical settings in the United States.  Pharmacists can be pivotal in educating others and employing strategies toward type 2 diabetes prevention.


  1. Diabetes Prevention Program Research Group, Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
  2. Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study [Erratum in Lancet. 2009;374:2054]. Lancet. 2009;374:1677-86.
  3. Ratner RE, Christophi CA, Metzger BE, et al.; Diabetes Prevention Program Research Group. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 2008;93:4774–4779.
  4. Aroda VR, Christophi CA, Edelstein SL, et al.; Diabetes Prevention Program Research Group.  The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program Outcomes.  Study 10-year follow-up. J Clin Endocrinol Metab 2015;100:1646–1653.
  5. American Diabetes Association. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes 2018.  Diabetes Care 2018;41(Suppl. 1):S13–S27.
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  8. Fox TV: Family Guy. McStroke: Season 6, Episode 9.  Full episode first aired on January 13, 2008.  Short clip:  Accessed 1/17/18.
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  12. Blonde L, Dailey GE, Jabbour S, Reasner CA, Mills DJ. Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study.  Curr Med Res Opin. 2004;20(4)565-72.
  13. Feher MD, Al-Mrayat M, Brake J, Leong KS. Tolerability of prolonged-release metformin (Glucophage) in individuals resistant to standard metformin—results from four UK Centeres.  Brit J Diabetes Vasc Dis. 2007; 225-228.
  14. Donnelly LA, Morris AD, Pearson ER. Adherence in patients transferred from immediate release metformin to a sustained release formulation: a population-based study.  Diabetes Obes Metab. 2009;11:338-342.
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How Sweet it Ain’t

Ah, it’s that time of year again. Turkeys getting stuffed, people getting stuffed and “leave room for dessert.” We love our sweets, and over time our sweet tooth has increased to where the average American eats 15-20 grams of sugar a day, primarily as sweet snacks or sugar sweetened beverages (Carbonated Soft Drinks -CSDs). (1) When we were young we worried about getting cavities, as we got older we worried about getting fat, but we still increased our sugar intake as we aged, and overall as our society aged. Over the years, children and adolescents increased their consumption of sugar sweetened beverages as more of them became available and more readily available in the ubiquitous ‘soda machines’. (2) Of course, ‘sugars’ are of different types, and how the body metabolizes the sugar in fruit and milk differs from how it metabolizes the refined sugar added to processed foods. For the sake of this discussion, ‘sugar’ (sucrose) is refined from sugar cane (to remove the molasses) or a sugar-like sweetener (High Fructose Corn Syrup -HFCS)produced as starch in corn is digested with heat and enzymes to make corn syrup. This process is very involved, requires heat, acid, multiple enzymes and a small amount of mercuric chloride. (3) The sweet syrup still contains some undigested oligosaccharides as well as 5-hydroxymethyl-2-furfural (HMF) which is a known toxin. HMF contents in both sucrose and HFCS are very high (406.6-2121.3 mg/kg for corn syrup and 109.2-893.1 mg/kg for cane syrup), which arouses concern about food safety of these products. (4) In addition, analysis of carbonated soft drinks (CSD) has shown significant degradation products of sugar components, namely -dicarbonyl compounds (5) which most of us associate with diabetes. There is clear evidence that dicarbonyl stress is a contributing mediator of obesity and vascular complications of diabetes. (6,7) While sucrose contains glucose and fructose, it seems that spiking additional fructose (as in HFCS) may not be a good idea since it has been associated with fatty liver and other biochemical changes. (8) We also know, that in many common CSDs there is even more fructose than you might believe from the use of HFCS as a sweetener (as high as 65%). (9) So now we know that the ‘sweetness’ we seek, may have some downsides, but is this new? It turns out that some of the issues uncovered with sugar experiments in rodents were somehow never fully completed in experiments or published. A recent article in JAMA Internal Medicine exposes a 1960s study, which suggests a link between a high-sugar diet and high blood cholesterol levels and cancer in rats, was sponsored by the sugar industry, and when initial findings were presented to the sponsor, the funding disappeared. (10). A more recent article from the same authors suggested that the Sugar Research Foundation sponsored a research program that successfully cast doubt about the health hazards of a high-sugar diet and rather promoted fat “as the dietary culprit” in health concerns such as heart disease. (11) So, there you have it! That is part of the reason the new dietary guidelines call for reducing sugar intake roughly in half. (12) Coca-Cola anyone?



2) Sugar sweetened Beverage Consumption Among U.S. Youth 2011-2014. Rosinger A, Herrick K, Gahche J, Park S. National Center for Health Statistics Data Brief No. 271, January 2017

3) High Fructose Corn Syrup

4) In house validation fro direct determination of 5-hydrosymethyl-2-furfural in corn and cane syrups samples by HPLC-UV. deAndrade JK, Komatsu E, Perreault H, Torres YR, daRosa MR, Felsner ML. Food Chem. 2016;190:481-486

5) Analysis of sugar degradation products with -dicarbonyl structure in carbonated soft drinks by UHPLC-DAD-MS/MS. Gensberger S, Glomb MA, Pischetsrieder M. J. Agri. Food Chem. 2013;61:10238-10245

6) Post-Glucose Load Plasma α-Dicarbonyl Concentrations Are Increased in Individuals With Impaired Glucose Metabolism and Type 2 Diabetes: The CODAM Study. Maessen DE, Hanssen NM, Scheijen JL, van der Kallen CJ, van Greevenbroek MM, Stehouwer CD, Schalkwijk CG. Diabetes Care. 2015;38:913-20

7) Dicarbonyls and glyoxalase in disease mechanisms and clinical therapeutics. Rabbani N, Xue M, Thornalley PJ. Glycoconj J. 2016;33:513-25.

8) Added fructose as a principal driver of non-alcoholic fatty liver disease: a public health crisis. DiNicolantonio JJ, Subramonian AM, O’Keefe JA. Open Heart. 2017; 4(2): e000631

9) Sugar Context of Popular Sweetened Beverages Based on Objective Laboratory Analysis: Focus on Fructose Content. Ventura EE, Davis JN, Goran MI. Obesity 2010;19:868-874

10)Sugar Industry and Coronary Heart Disease research: A historical analysis of internal industry documents. Kearns CE, Schmidt LA, Glantz SA. JAMA Intern. Med. 2016;176:1680-1685

11) Sugar industry sponsorship of germ-free rodent studies linking sucrose to hyperlipidemia and cancer: An historical analysis of internal documents. Kearns CE, Appolonio D, Glantz SA. PLoS Biol. 2017;15:e2003460

12) Dietary Guidelines for Americans: 2015-2020 (Accessed 11/25/17)