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Management Options
A 55-year old Caucasian woman has been under your care for three years. Eighteen months ago you diagnosed her with type 2 diabetes mellitus (T2DM). She has a history of mild hypertension, hypercholesteremia, and retinopathy.
However, she has no history of microalbuminuria, neuropathy, or cardiovascular events and reports no cardiac symptoms.
When you diagnosed her with T2DM, you initiated her on metformin (500 mg b.i.d.) and, because she was obese, advised her to lose weight through specific dietary changes and a commitment to a regular walking program of 30 minutes per day. Since then you have seen her twice (every six months) and have increased her dosage each time because her HbA1c has remained above 7.0%. During these subsequent visits she reported intermittent success with modest weight loss, losing 10-15 pounds but repeatedly regaining it. For the past six months, she has been on a maximally effective dose of metformin (1,000 mg b.i.d.). Additionally, she is taking hydrochlorothiazide (25 mg daily) and lisinopril (20 mg daily) for her hypertension, simvastatin (20 mg daily) for her hypercholestermia, and aspirin (81 mg daily) for cardioprotection. She reports taking these medications consistently.
The patient’s HbA1c is 7.6%, which is an increase from 7.2% six months ago, and her fasting blood glucose level was 163 mg/dl and ranges between 150 and 170 mg/dl. Her LDL, HDL, and triglycerides are in target range. Additional lab tests show normal results for thyroid, renal, and liver function.
Your recent physical examination shows normal cardiorespiratory, abdominal, and neurologic findings. With medications, her blood pressure measured 128/78 mmHg. A recent ophthalmic exam confirmed mild, non-proliferative retinopathy.
Presently her BMI (body-mass index) is 31 kg/m2. She reports only being able to walk occasionally during the week due to work and family obligations but says she walks most weekends when the weather is good.
The patient has health insurance through her employer, which includes prescription drug coverage. She is seeking advice about the management of her diabetes.
Treatment Options
Which one of the following treatment options do you think would be most appropriate for this patient?
1. Add a sulfonylurea (SU)
2. Add a thiazolidinedione (TZD)
3. Add an incretin therapy (GLP-1 agonist or DPP-4 inhibitor)
Continue to Management Options
Sulfonylurea (SU)
Charles R. McClave II MD FACP
Saint Vincent Healthcare Diabetes Center
Billings, Montana
This 55-year-old woman has had documented type 2 diabetes for 18 months but already has early diabetic retinopathy, indicating she has had metabolic issues for a much longer time and is likely to develop further complications if her control is not improved. At this stage of her disease, she is clearly still secreting insulin, but not enough to maintain euglycemia by meeting insulin demands. By stimulating her endogenous insulin secretion, sulfonylureas will likely provide enough additional circulating insulin to control her glucose levels, at least for a period of time. The average decrease in hemoglobin A1c that can be expected from these medications is 1-2%, which should be enough to lower below 7%, the current ADA recommended target. [1]
Glucose Lowering Effects of Sulfonylureas
Sulfonylureas work by binding to the sulfonylurea binding site (sulfonylurea receptor, or SUR) on the β-cell wall, triggering the closure of potassium channels and consequent membrane depolarization, calcium channel opening, and calcium influx. The resultant increase in intracellular calcium triggers insulin release. Sulfonylureas in current common use include glyburide, glimeparide and glipizide. Of these, glyburide has the strongest receptor affinity, with glimeparide and glipizide following in that order.
Table 1 summarizes the characteristics of these drugs, but a few points are worth additional emphasis. First, comparing the half-lives of these drugs is somewhat misleading due to the formation of inactive metabolites. [2] The hypoglycemic effects of both glyburide and glimeparide can be observed for more than 24 hours. In addition, the clinical frequency of hypoglycemia is highest with glyburide, with glimeparide and glipizide following. Because of their long durations of effect, glyburide and glimeparide are most effective in lowering fasting plasma glucose. This potential benefit has to be weighed against the increased risk of hypoglycemia. [3]
Table 1 Characteristics of “second generation” sulfonylureas
For the patient under discussion, any of these medications could be used. Since her fasting glucose is significantly elevated, one of the longer acting, more potent medications might be most appropriate. Due to the relatively high incidence of hypoglycemia associated with glyburide, I would probably choose glimeparide, beginning with a dose of 1 mg each morning. My own preference when adjusting diabetic medication is to have the patient measure fingerstick glucose four times daily, before each meal and at bedtime. We have the patient provide us glucose records on a weekly basis, titrating the drug upward at weekly intervals until control is reached. The frequent glucose monitoring provides a measure of protection against hypoglycemia, and also frequently provides the patient with useful information about the glycemic effect of meal and snacking habits. As control tightens, it is often useful to have the patient check during the night as well to detect any nocturnal hypoglycemia. Typically, control is likely to be achieved with no more than 4 mg glimeparide as a daily dose, unless there is marked insulin resistance. If glipizide is chosen, I typically start with 2.5 -5 mg in the morning, increasing to twice daily dosing when the dose exceeds 10 mg. Doses above 20 mg per day, particularly if the XL preparation is used, rarely add much more effect in my experience.
Sulfonylurea Therapy as a Stopgap Measure
There may be two immediate problems with sulfonylurea therapy in this patient, regardless of the agent chosen. The first, already touched on, is the potential for hypoglycemia. One of the reasons I have patients test four times daily is that it helps to predict when hypoglycemia is most likely to occur, so that the patient can be properly educated. In my experience, individuals with type 2 diabetes fall into one of three categories. Many have sustained hypoglycemia throughout the day and night, but some have relatively good fasting sugars with deterioration when they eat, and a smaller number will have their biggest problem with high fasting sugars, which actually improve with the ingestion of food and increased activity during the day. Those with good fasting sugars will be most prone to nocturnal hypoglycemia with sulfonylureas. These patients have their greatest difficulty processing ingested carbohydrate, as opposed to controlling nighttime hepatic glucose production. If they have severe nocturnal hypoglycemia on sulfonylureas, an alternative choice might be repaglinide or nateglinide—short acting, non-sulfonylurea insulin secretagogues. Patients with high fasting sugars and improved daytime sugars will be most prone to hypoglycemia during the day, particularly with exercise, and should be cautioned accordingly.
A second immediate problem with sulfonylurea therapy in this patient will be the tendency to gain weight. There may be several reasons for this. With fasting sugars in the 160 range, it is likely that postprandial sugars will exceed 200 mg/dl which will result in some degree of glycosuria. To consider net 24-hour caloric intake, calories lost in the urine must be subtracted from total dietary intake. If the net caloric intake results in a stable weight prior to treatment, lowering the glucose and eliminating urinary loss with medication (regardless of type) will result in a net increase in 24-hour calorie consumption. If the patient does not restrict her intake when the sulfonylurea is started, successful glucose control will result in further weight gain. If hypoglycemia is occurring due to therapy, moreover, forcing the patient to eat additional food compounds the problem.
A long-term problem associated with sulfonylurea use is the loss of effectiveness with time. The UKDPS study demonstrated that insulin production progressively declines over a period of years, regardless of the type of therapy, in fact. [4] We now know this problem of durability occurs because of progressive loss of β-cell mass, for reasons that are not entirely clear. Sulfonylureas, while effective in the short run, do nothing to address this problem.
Given these challenges, sulfonylurea therapy in this patient should be regarded as a stopgap measure to control glucose for the next year or two. If coupled with aggressive emphasis on caloric restriction and increasing daily exercise it may be successful for a substantially longer period. When using these drugs, I also believe it is essential to emphasize to this patient the need for lifestyle changes, warning her that she may well require insulin or other medications in the near future if no changes are made. I would also recommend follow-up at least four times per year for monitoring, encouragement, and A1c determinations. The more attention we as physicians pay to our patients’ diabetes, the more likely they are to modify behavior.
Summary
Tight control of glucose has been shown to reduce microvascular complications of diabetes; the current American Diabetes Association recommended target is <7%. Given this patient’s history and clinical findings, sulfonylurea, a highly cost-effective class of drugs, could be used as a second-line therapy to improve glucose control in light of their known ability to reduce hemoglobin A1c levels 1-2%. Because sulfonylureas do not address the underlying problem of β-cell loss, however, they will probably only serve as a stopgap therapy. In addition, any clinician prescribing these drugs must consider the hypoglycemia and weight gain associated with the sulfonylureas and arrange for frequent office followup, including A1c determinations and aggressive attempts to encourage lifestyle modifications and weight loss.
See below for References and Disclosures.
References
1. Standards of medical care in diabetes—2010. Diabetes Care 2010; 33 Suppl 1:S11.
2. Rydberg T; Jonsson A; Roder M; Melander A. Hypoglycemic activity of glyburide (glibenclamide) metabolites in humans. Diabetes Care 1994 Sep;17(9):1026-1030.
3. Shorr RI; Ray WA; Daugherty JR; Griffin MR. Individual sulfonylureas and serious hypoglycemia in older people. J Am Geriatr Soc 1996 Jul;44(7):751-755.
4. Turner RC; Cull CA; Frighi V; Holman RR.Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999 Jun 2;281(21):2005.
Disclosure:
Disclosure information to come.
Thiazolidinedione (TZD)
David M. Kendall
International Diabetes Center
Minneapolis, MN
For this patient, persistent evidence of insulin resistance could arguably warrant adding a thiazolidinedione (TZD) as a second line treatment option. This patient is characteristic of so many patients we see with type 2 diabetes, be it of shorter or longer duration. While the initial approach to care was reasonably successful, with significant reductions in A1C accompanying the changes in lifestyle, glucose treatment targets recommended for the general population (<7%) were not achieved. The patient has been monitored with regular blood glucose testing (also above target with most values averaging >140 mg/dl) and A1C testing at least twice per year. The gradual increase in A1C values suggests that the time for added therapy is now. However, choosing the most appropriate drug class for treatment remains a challenge, given that many classes of diabetes therapy (when added to metformin) work very well. Differentiating these choices requires a better understanding of the potential benefits of each class of treatment and its impact on both the progressive nature of diabetes and the potential associated risks Control of co-morbidities may be of importance when selecting additional glucose lowering therapy as well.
Early Use of Combination Therapies
While many would suggest that more time is needed to assess the response to this simple, safe, and effective treatment approach (metformin) in this patient, myriad studies have shown us the progressive nature of type 2 diabetes. The gradual increase in A1C seen in this case is indicative of that progression, and suggests further deterioration in b-cell secretory function. Much of our clinical experience suggests that early use of combination therapies would be more effective in a patient like this than the current approach, together with regular follow-up of other CVD risk factors (blood pressure, lipids, and aspirin use where appropriate), which, in addition to monitoring glycemic control, are of paramount importance in managing type 2 diabetes.
The figure below (from the International Diabetes Center) outlines one such approach to second line treatment decisions—and emphasizes the central role of metformin therapy (where appropriate) and the most common choices for second line treatment.
TZD as a Second Line Treatment Option
In this case, our 55-year-old patient warrants further attention to CVD risk factors given that she has known dyslipidemia and hypertension. Her increased body mass index suggests that additional weight loss may be of benefit as well, but even early weight loss has not addressed her medical and clinical needs. As shown in the figure above, however, the persistent evidence of insulin resistance (as marked by the presence of obesity and/or mixed dyslipidemia) suggests that using TZD as second line therapy may well help the patient meet glycemic targets and further improve lipid parameters .
TZDs have been widely used in combination with many other glucose lowering therapies. They are effective when used in combination with other anti-hyperglycemic medications (such as metformin, DPP-4 inhibitors or GLP-1 agonists), and carry a very low risk of hypoglycemia. Data from a number of studies—including clinical trials and early intervention trials in diabetes (e.g., ADOPT and ACT Now) have suggested that TZD therapy may provide greater stability in glycemic control and improve surrogate measures of B-cell function. One recent review (Defronzo) [1] compared the effects of TZD to sulfonylurea therapy and suggested an improved capacity to maintain glucose control with TZD therapy. In addition, the TZD pioglitazone has been shown to improve plasma lipids—with predominant effects on HDL-c and triglycerides. Pioglitazone has also been shown to lower the risk of major CVD events, although the ProACTIVE study failed to reduce all combined CV events. [2]
Potential adverse effects of TZD therapy would include the potential for weight gain (despite improved insulin sensitivity) and a risk for fluid retention. More serious but unusual adverse effects include a higher risk of heart failure and a still poorly understood increase in long bone fracture risk. More recently, a number of questions have been raised regarding the overall cardiovascular safety of TZD therapy—with some analyses suggesting that treatment with rosiglitazone (but not pioglitazone) may increase the risk of major cardiovascular events, particularly myocardial infarction. Ongoing safety surveillance and randomized comparative trials have not demonstrated definitive risk, but a large head-to-head study (TIDE) comparing the effects of rosiglitazone to pioglitazone is ongoing.
Summary
The progressive nature of type 2 diabetes (and accompanying decline of b-cell function) support early use of combination therapies–generally including metformin therapy, which are often necessary to overcome the progressive β-cell failure seen in type 2 diabetes. While still broadly utilized, neither metformin, nor lifestyle changes, have been shown to interrupt this disease progression. Many choices for second (and third) line therapy now exist, and second line treatment choices can be guided by both the effects (and side effects) of therapy as well as by specific patient characteristics (such as CV risk, body weight, other risk factors, tolerability, and cost). In this case, a good argument can be made for insulin sensitizing therapy with second line TZD therapy directed specifically at improving insulin action (and reducing insulin resistance). Regardless of treatment choice, regular interval follow-up will be necessary to assure the adequacy of therapy and to monitor for treatment-associated adverse effects, as well as to support patient adherence.
See below for References and Disclosures.
Comments
Posted 10/23/10 by Amelio Godoy-Matos
TZDs have demonstrated its value in several long-term studies. In fact, even understanding this is an obese patient, those are insulin resistant the most. Moreover, weight gain from TZDs is not harmful itself due to fat re-distribution. I have recently published an study showing a decrease in intra-to-extramiocellular fat ratio in MS patients under rosiglitazone, despite ~7kg increase in body weight after 6 months (Godoy-Matos A et al. Diab Med 2010;27:23-29). However, I would strongly consider a triple combination including incretin based therapy. Importantly, to minimizing side effects I'd suggest low daily dose of a TZD (30mg pioglitazone). In conclusion, pathophysiologic approach with 3 drugs to recover/preserve beta-cell seems to be the best option in this case.
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References
1. Defronzo RA 2009 Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58:773-795.
2. Charbonnel B, DeFronzo R, Davidson J, et al. Pioglitazone use in combination with insulin in the prospective pioglitazone clinical trial in macrovascular events study [PROactive19]. J Clin Endocrinol Metab. 2010 May;95(5):2163-2171. Epub 2010 Mar 17.
Disclosure:
Research support: Amylin Pharmaceuticals, Dexcom, Eli Lilly and Co, Medtronic/MiniMed, Merck, NIH-NHLBI, Novo Nordisk, Roche, Sanofi-Aventis
Consultant, Scientific and Clinical Advisory Board or Safety oversight activity and Educational Funding: Amylin Pharmaceuticals, Bayer Diabetes Care, Daiichi-Sankyo, Eli Lilly and Co., HealthPartners, Intarcia, Merck, Roche Genentech, Takeda, UnitedHealth Group
Employment: Spouse current employee of Genentech (Roche)
All industry sponsored research activity, advisory/consultancy work and educational services were performed under contract directly to the non-profit Park Nicollet Institute and the International Diabetes Center in 2008-2009 and Dr. Kendall received no personal or direct compensation for these activities.
Dr. Kendall is currently Chief Scientific and Medical Officer of the American Diabetes Association (ADA). The views and opinions presented are his own, and do not necessarily reflect an official position of the ADA.
Glucagon-like peptide 1 (GLP-1)
David A. D’Alessio, MD
University of Cincinnati College of Medicine
Cincinnati, Ohio
This patient is emblematic of the large number of Americans with multiple risk factors for premature cardiovascular disease, including type 2 diabetes. While the specific mechanisms of disease in such patients are still being defined, the increasing prevalence of overweight and obesity certainly contributes to higher rates of metabolic and vascular abnormalities. This woman’s management has met the current standards for care, and her success, albeit transient, in weight loss suggests that she has been compliant with treatment recommendations. The recent increase in A1c to 7.6 appears at first glance to be only modest, but given her efforts at lifestyle management and presumed regularity with her medications likely portends the onset of monotherapy failure. Therefore, increased diabetes therapy, to maintain an A1c target of 7.0, is a reasonable next step.
One of the major advances in diabetes therapeutics over the past decade has been the introduction of medications that act through the endogenous glucagon-like peptide 1 (GLP-1) receptor signaling system. [1] GLP-1 is an intestinal hormone, termed an incretin because it stimulates insulin secretion, that is essential for normal glucose tolerance. Two classes of incretin-based drugs are now available. GLP-1 receptor (GLP-1r) agonists are injectable peptides that stimulate the range of actions mediated through the GLP-1 system. Dipeptidyl peptidase 4 (DPP-4) inhibitors are oral agents that block the rapid degradation of GLP-1, prolonging the action of the native hormone and increasing plasma levels by 2-3 fold. Either of these classes of drugs could be effective in the patient presented here who is drifting away from her glycemic target.
GLP-1r Agonists Versus DPP-4 Inhibitors
GLP-1r agonists, such as exenatide, liraglutide and several others in development, provide pharmacologic plasma concentrations of GLP-1 equivalency, far above the physiologic levels achieved by endogenous secretion. Thus, these drugs engage most of the responses affected by GLP-1r activation, most importantly increased insulin secretion, reduced glucagon release, delayed gastric emptying, and satiation/satiety. [2] The end result of these actions is improved glycemic control and, frequently, weight loss. This latter effect is unique among currently available drugs for diabetes and is generally a key element in the decision to use a GLP-1r agonist. For the woman described in this case, starting exenatide or liraglutide would be expected to reduce her A1c by 0.8-1.2% and her weight by up to 3-5 kg. [3] For a patient frustrated by the usual fluctuating outcomes with diet and exercise the effects of GLP-1r agonists to reduce food intake could be a welcome benefit.
Like GLP-1r agonists, DPP-4 inhibitors have positive effects on the diabetic islet with increased insulin and decreased glucagon release. [4] However, these agents do not affect GI motility or food intake and do not cause weight loss. On the other hand they reduce A1c 0.8-1.0% and the improved glycemic control is not associated with weight gain. The hallmark of the DPP-4 inhibitors is their safety and tolerability. Agents such as sitagliptin, vildagliptin and saxagliptin have not been reported to have consistent major toxicities or drug interactions. [5] Like GLP-1r agonists, these medications are effective when added to metformin or other oral agents, and would be a safe and simple means of addressing this patient’s current shortcomings in diabetes control.
Neither GLP-1r agonists, nor DPP-4 inhibitors, have been associated with serious risk of hypoglycemia. This is due in large part to the glucose-dependent mechanism by which GLP-1 increases insulin secretion; infusions of the native hormone or pharmacologic analogs have minimal insulinotropic activity at fasting glucose levels. Although hypoglycemia is not often a major complication of therapy in obese, middle-aged diabetic patients, this feature of incretin-based drugs offers a relative advantage over therapies such as sulfonylureas, meglitinides or insulin.
Side Effects and Contraindications
While generally safe, GLP-1r agonists have several side effects. Nausea, and occasionally vomiting, occur in nearly half of patients with the onset of therapy. [6] This is likely due to activation of CNS nausea centers that are responsive to GLP-1r activation, and the result of supraphysiologic plasma levels of the agonist. With dose titration and development of tolerance to the illness-inducing effects of the drugs, the GI side effects of exenatide and liraglutide wane in most patients. There has been a recently noted association of pancreatitis with exenatide therapy. [7] This is rare and the mechanism unclear, but drugs that activate the GLP-1r should not be used in patients with pancreatitis.
There are several important caveats to the routine use of GLP-1-based drugs (incretin mimetics). These are still new compounds, and long-term outcomes of their use are not well established. Moreover, there is not yet good post-approval trial data to define the niche of GLP-1r agonists or DPP-4 inhibitors in treatment algorithms. Finally these are expensive drugs: retail costs for DPP-4 inhibitors and exenatide are generally $100-200 per month, and liraglutide is more than $200 monthly.
Summary
In the case described here, an obese woman with type 2 diabetes shows evidence of failure of metformin therapy. The addition of an incretin-based treatment is a reasonable way to get her A1c to goal while minimizing weight gain or even inducing some weight loss. In this case, the struggle with her weight makes a GLP-1r agonist the better choice, provided she accepts one or two daily injections. Her sound insurance coverage will mitigate the substantial costs of these medications.
See below for References and Disclosures.
Comments
Posted 2/20/13 by alfredo halpern
For sure the best drug to be added to this patient is GLP1 Agonist.To loose weight is a very difficult task for all,and particularly for patient s with DM2 and GLP1 Agon. help a lot for this and for the glycemic control.
Posted 1/18/13 by Robert J Simon, MD
I agree with addition of the GLP1 agonist since this patient is obese and weight loss would be extremely helpful in lowering her HbA1c. Furthermore, the decrease in appetite observed with GLP1 agonists would lead to decreased intake and further lower serum glucose levels. While I am a strong fan of TZDs and agree that th progression of diabetes is slowed by these medications, this patient has so far avoided sequelae. Furthermore, TZDs, at least in my experience, not only add weight, but also reduce the ability of patients to lose weight on even strict diets. Sulfonylureas might lower blood sugars but in the long-run as they stimulate the pancreas into failure and have significant potential for hypoglycemia. If I am interested simply in lowering blood sugar, insulin would be a better choice.
Posted 7/27/10 by Eugene Wright
This patient is typical of many patients who have despite very good efforts with lifestyle changes and Metformin, been unable to achieve or sustain HbA1c of<7%. The use of the the GLP 1 agonists have been beneficial to our patients for weight and A1c management without the risk of hypoglycemia. They are generally well tolerated and the total cost of care over time I believe is improved.
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References
1. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368:1696–1705.
2. Baggio L, Drucker J. Biology of incretins: GLP-1 and GIP. Gastroenterol 2007;132:2131–2157.
3. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and metaanalysis. JAMA 2007;298:194–206; Drab SR. Incretin-based therapies for type 2 diabetes: Current status and future prospects. Pharmacotherapy 2010;30:609-624.
4. Drab SR. Incretin-based therapies for type 2 diabetes: Current status and future prospects. Pharmacotherapy 2010;30:609-624.
5. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and metaanalysis. JAMA 2007;298:194–206; Drab SR. Incretin-based therapies for type 2 diabetes: Current status and future prospects. Pharmacotherapy 2010;30:609-624.
6. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and metaanalysis. JAMA 2007;298:194–206; Drab SR. Incretin-based therapies for type 2 diabetes: Current status and future prospects. Pharmacotherapy 2010;30:609-624.
7. Ahmad SR, Swann J. Letter in NEJM 2008;358:1970-1971.
Disclosure:
David D'Alessio has provided consultancy to Merck, Novo Nordisk, Ethicon, Mannkind, Wyeth, and Amylin, and has received research grants from Lilly, Ethicon, and Sanofi.
Cast a vote to see the results.
Option #3
Posted 2/20/13 by alfredo halpern
For sure the best drug to be added to this patient is GLP1 Agonist.To loose weight is a very difficult task for all,and particularly for patient s with DM2 and GLP1 Agon. help a lot for this and for the glycemic control.
Option #1
Posted 9/26/10 by Yung-In Choi
I would add basal insulin either insulin glargine or detemir at dinner time to keep the fasting glucose in normal range and have her see a RD, CDE for medical nutrition therapy counseling. I will start 20% of her body wt in Kg as the starting unit of the insulin and have patient upregulate the insulin by 10% daily until the fasting glucose is below 130 mg/dL and downregulate 10% the same day if the fasting glucose is below 90 mg/dL.
Option #3
Posted 1/18/13 by Robert J Simon, MD
I agree with addition of the GLP1 agonist since this patient is obese and weight loss would be extremely helpful in lowering her HbA1c. Furthermore, the decrease in appetite observed with GLP1 agonists would lead to decreased intake and further lower serum glucose levels. While I am a strong fan of TZDs and agree that th progression of diabetes is slowed by these medications, this patient has so far avoided sequelae. Furthermore, TZDs, at least in my experience, not only add weight, but also reduce the ability of patients to lose weight on even strict diets. Sulfonylureas might lower blood sugars but in the long-run as they stimulate the pancreas into failure and have significant potential for hypoglycemia. If I am interested simply in lowering blood sugar, insulin would be a better choice.
Option #1
Posted 8/24/10 by Karen Agersborg
Couldn't agree more with the TZD and GLP-1 agonist. The patient has insurance so why use a suboptimal drug. Her main dysfunction is insulin resistance as as defined by her fasting blood sugar of 160 mg/dL and obesity.
Option #3
Posted 7/27/10 by Eugene Wright
This patient is typical of many patients who have despite very good efforts with lifestyle changes and Metformin, been unable to achieve or sustain HbA1c of<7%. The use of the the GLP 1 agonists have been beneficial to our patients for weight and A1c management without the risk of hypoglycemia. They are generally well tolerated and the total cost of care over time I believe is improved.
Option #2
Posted 10/23/10 by Amelio Godoy-Matos
TZDs have demonstrated its value in several long-term studies. In fact, even understanding this is an obese patient, those are insulin resistant the most. Moreover, weight gain from TZDs is not harmful itself due to fat re-distribution. I have recently published an study showing a decrease in intra-to-extramiocellular fat ratio in MS patients under rosiglitazone, despite ~7kg increase in body weight after 6 months (Godoy-Matos A et al. Diab Med 2010;27:23-29). However, I would strongly consider a triple combination including incretin based therapy. Importantly, to minimizing side effects I'd suggest low daily dose of a TZD (30mg pioglitazone). In conclusion, pathophysiologic approach with 3 drugs to recover/preserve beta-cell seems to be the best option in this case.
Option #1
Posted 8/2/10 by Dr. Chris Rhodes
Not sulfonylurea (SU), I think this would add extra pressure to a hard working beta-cell attempting (best it can) to compensate for the increased metabolic load and insulin resistance by secreting more insulin without replenishing internal stores of insulin. A close call between Thiazolidinedione (TZD) and Glucagon-like peptide 1 (GLP-1). The TZD would likely alleviate some insulin resistance taking some pressure off the beta-cells, but went with the latter as there might be some additional beneficial 'insulin sensitizing' effects with some weight loss by GLP-1. Although GLP-1 would enhance insulin secretion like SU, it also increases insulin production in parallel (unlike SUs) so that beta-cell secretory capacity is maintained.
Option #1
Posted 9/2/10 by Jessica Triay
In view of her suboptimal control, weight issues and demographic, at this stage a GLP-1 agonist does seem to the the preferred choice. I think we do need to consider, however, that we still do not know the long term effects of these drugs, and rather like the TZD's (i.e. cardiovascular risk, long bone fracture), there may be future findings that change our prescribing habits yet again. I think we need to be frank with our patients about this when prescribing newer medications
Comments
No doubts thai a GLP1 Agonist is the first choice
I would add basal insulin either insulin glargine or detemir at dinner time to keep the fasting glucose in normal range and have her see a RD, CDE for medical nutrition therapy counseling. I will start 20% of her body wt in Kg as the starting unit of the insulin and have patient upregulate the insulin by 10% daily until the fasting glucose is below 130 mg/dL and downregulate 10% the same day if the fasting glucose is below 90 mg/dL.
Couldn't agree more with the TZD and GLP-1 agonist. The patient has insurance so why use a suboptimal drug. Her main dysfunction is insulin resistance as as defined by her fasting blood sugar of 160 mg/dL and obesity.
Not sulfonylurea (SU), I think this would add extra pressure to a hard working beta-cell attempting (best it can) to compensate for the increased metabolic load and insulin resistance by secreting more insulin without replenishing internal stores of insulin. A close call between Thiazolidinedione (TZD) and Glucagon-like peptide 1 (GLP-1). The TZD would likely alleviate some insulin resistance taking some pressure off the beta-cells, but went with the latter as there might be some additional beneficial 'insulin sensitizing' effects with some weight loss by GLP-1. Although GLP-1 would enhance insulin secretion like SU, it also increases insulin production in parallel (unlike SUs) so that beta-cell secretory capacity is maintained.
In view of her suboptimal control, weight issues and demographic, at this stage a GLP-1 agonist does seem to the the preferred choice. I think we do need to consider, however, that we still do not know the long term effects of these drugs, and rather like the TZD's (i.e. cardiovascular risk, long bone fracture), there may be future findings that change our prescribing habits yet again. I think we need to be frank with our patients about this when prescribing newer medications
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