Diabetes is Primary 2014 - A Diabetes Core Update Special Edition: New Therapies

Summary

Diabetes Core Update – Special Edition: New Therapies (June 25, 2014)

Overview

This special episode of Diabetes Core Update is focused on "New Therapies" for type 2 diabetes, highlighting recent advancements and challenges in diabetes pharmacotherapy. Dr. Neil Skolnik and Dr. John Russell host Dr. Carol Wisham, Clinical Associate Professor of Medicine at the University of Washington, who shares insights from her presentation at the ADA’s “Diabetes is Primary” conference (June 2014 Scientific Sessions). The discussion covers new medications introduced in the previous year, including a once-weekly GLP-1 receptor agonist, SGLT2 inhibitors, and a new inhaled insulin formulation. Emphasis is placed on clinical characteristics, safety, patient communication, and the evolving landscape of individualized therapy.

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Key Discussion Points & Insights

1. The Need for New Therapies in Type 2 Diabetes

• Traditional therapies have limitations: increased risk of hypoglycemia, weight gain, and limited long-term control ([01:00]).
• Clinical trials highlight these shortcomings, driving innovations toward safer, more sustainable options that avoid hypoglycemia and weight gain.

"There has been a drive to try to develop medications that can help effectively lower glucose, avoid weight gain and hypoglycemia."
—Dr. Carol Wisham, [01:41]

2. The Once-Weekly GLP-1 Receptor Agonist: Albiglutide

• Albiglutide is a new, once-weekly GLP-1 receptor agonist offering enhanced convenience and tolerability ([03:29]).
• Mechanism: Boosts insulin secretion, suppresses glucagon, decreases appetite—thus typically weight-neutral or even inducing mild weight loss.
• Comparative effectiveness: Equivalent to exenatide twice daily for A1C lowering; possibly less effective than liraglutide; better GI tolerability but may confer less weight loss.
• Clinical benefits include improved adherence potential and fewer GI side effects due to the slow rise to steady state levels ([04:15]).

"The advantage of giving a medication once weekly is obvious... better GI tolerability than either of the medications and perhaps isn't associated with quite as much weight loss."
—Dr. Carol Wisham, [04:12]

3. SGLT2 Inhibitors: A New Class

• Function: Blocks renal glucose reabsorption, leading to glycosuria and reduced blood glucose ([05:35]).
• Benefits: Effective at many stages of disease (independent of insulin), oral administration, low risk of hypoglycemia, modest weight loss, and preferable for patients wanting to avoid injections.
• Side effects: ~10% vaginal yeast infection rate in women; slight increase in urination and possible mild volume depletion (especially on starting therapy); modest bump in LDL cholesterol as a class effect ([06:45], [08:09]).
• Drugs in this class include dapagliflozin and canagliflozin; not studied directly head-to-head, but similar side effect profiles.

"Patients will opt for the meds that don't cause weight gain and don't cause hypoglycemia… they tend to gravitate towards the SGLT2 inhibitors."
—Dr. Carol Wisham, [09:50]

• Patient-centered approach: Dr. Wisham stresses collaborative decision-making, providing "bullet points" on pros and cons—including cost—to support patient choice ([08:55]).

4. Inhaled Insulin: Technosphere Insulin

• An FDA advisory panel has recently approved a new inhaled insulin formulation—technosphere insulin ([10:31]).
• Advantages over previous inhaled insulins:
  • Exists as insulin monomers (not hexamers), yielding quicker absorption and faster action
  • Smaller inhaled particles for more efficient systemic uptake
  • Can replace rapid-acting, prandial insulin requirements for both type 1 and type 2 diabetics—though not a substitute for basal insulin ([10:45]).
  • Improved convenience (especially outside the home) and social acceptability relative to injections.

"They would just take an inhalation of insulin before they sit down to have their meal."
—Dr. Carol Wisham, [11:22]

• Fewer concerns about pulmonary toxicity compared to earlier inhaled insulins; though a mild cough in some patients is possible ([12:19]). Safety profile is reported as reassuring.

5. Communicating Medication Risks with Patients

A. Incretin Therapy & Pancreatic Risks ([12:53])

• Patients often worry about pancreas safety with incretin-based therapies (GLP-1 agonists, DPP-4 inhibitors).
• Dr. Wisham’s approach:
  • Explains FAERS database limitations and reporting biases
  • References large studies that have not found excess risk with incretin therapies
  • Informs of pancreatitis symptoms, urges vigilance, and offers reassurance drawn from clinical trial and real-world experience

"I just reassure them using these medications for now, over 12 years... I’ve not seen any cases of pancreatitis happen related to the medication."
—Dr. Carol Wisham, [14:10]

B. SGLT2 Inhibitors: Risks & Patient Management ([16:41])

• Candid, practical advice on managing SGLT2-associated risks:
  • Educates about possible vaginal yeast infections, usually single episodes; hygiene tips provided
  • Reviews blood pressure and adjusts antihypertensive or diuretic therapy accordingly
  • Stresses hydration, especially at therapy initiation
  • For patients on insulin or sulfonylureas: considers dose reduction to avoid hypoglycemia due to rapid action

"This medication works the day they take it… they can tell that they're lowered immediately. It works that fast."
—Dr. Carol Wisham, [18:17]

6. The Value of Individualized, Patient-Driven Therapy ([15:24])

• Emerging data shows improved adherence and satisfaction when patients are actively involved in selecting their regimen.
• Dr. Wisham recommends ongoing communication: patients are encouraged to report issues early so therapy can be adjusted promptly.
• Flexibility and choice enhance comfort, ownership, and outcomes.

"Having patients choose the medications they're interested in when I give them the option kind of takes some of that concern away."
—Dr. Carol Wisham, [14:51]

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Notable Quotes & Memorable Moments

• On the personalized approach:

  "You have to move on and then say, okay, here's some other options for you... having patients choose the medications they're interested in... they're generally very comfortable with it when they leave the office."
  —Dr. Carol Wisham, [14:51]

• On adherence and patient comfort:

  "Telling patients what to expect, telling them to drink plenty of fluid as you get started ... has resulted in... a very significant proportion of patients. Patients have been very successful at improving their glucose control."
  —Dr. Carol Wisham, [07:01]

• On new medicines’ impact for primary care:

  "It's probably one of the areas of medicine that has the largest amount of research making it really very exciting for primary care physicians since it's a common thing that we take care of, but also very challenging to keep up with all the new medicines."
  —Dr. John Russell, [03:05]

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Timestamps for Important Segments

• [01:00] – Rationale for driving new medication development in diabetes
• [03:29] – Introduction and characteristics of once-weekly GLP1 agonist (albiglutide)
• [05:39] – Mechanism and clinical use of SGLT2 inhibitors
• [07:49] – Safety, class comparison, and patient preferences in SGLT2 selection
• [10:31] – Introduction and clinical implications of technosphere inhaled insulin
• [12:53] – Communicating risk of pancreatitis with incretin agents
• [16:41] – SGLT2 inhibitor side effects and practical counseling pearls
• [15:24] – The role of patient choice in therapy adherence and satisfaction

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Conclusion

This episode provides a concise and authoritative review of groundbreaking advances in diabetes therapy, emphasizing practical considerations, risk counseling, and, above all, individualized patient care. Dr. Wisham’s insight underscores the importance of patient engagement and the rapidly evolving options available to primary care clinicians managing type 2 diabetes.

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For more information and further reading, visit: www.diabetesjournals.org

Transcript

[A]

Hello, I'm Dr. Neil Skolnick and I'd like to welcome you to a special edition of Diabetes Core Update. On this podcast, we will be interviewing a number of the faculty who are presenting during the American Diabetes Association Scientific Sessions Diabetes is primary conference on June 14, 2014. On today's podcast, we will be hearing highlights of a talk given by Dr. Carol Wisham on new therapies and communicating medication risks. Dr. Wishom is a clinical associate professor of medicine at the University of Washington.

[B]

Welcome, Dr. Wisham.

[C]

Thank you.

[B]

Can you talk to us a little bit about the discussion that you're having on new therapies and the need for new therapies in type 2 diabetes?

[C]

The Conversation or the subject that I plan to cover during the presentation is to review medications that are new over the course of the last 12 months to the time that we're going to be giving the presentation, which includes one new medication within the class of the SGLT2 inhibitors. It also includes discussion of a new GLP1 receptor agonist and then finally going to be talking about a new inhaled insulin product. The continuous drive to develop new medications with diabetes has been really driven by the failure of traditional therapies to achieve long term glucose control in a safe manner. We're recognizing because of several large clinical trials that were published within this last decade that traditional therapies are associated with increasing hypoglycemia rate, increasing risk for weight gain, and have potentially limited our ability to provide our patients with good long term control of diabetes, as well as perhaps increasing complications related to the therapies themselves, that is the weight gain and hypoglycemia. So there has been a drive to try to develop medications that can help effectively lower glucose, avoid weight gain and hypoglycemia. Unfortunately, as you know, medications only have a certain amount of durability in terms of ability to lower glucose levels as the diabetes progresses. And so we need to be adding on additional medications over time in order to keep the glucose control at an optimal range and hence looking for new therapies that we can safely add on to metformin and beyond that will give our patients ultimately good control and decrease their complication rate.

[B]

It's really fortunate because it's probably one of the areas of medicine that has the largest amount of research making it really very exciting for primary care physicians since it's a common thing that we take care of, but also very challenging to keep up with all the new medicines. Why don't we start with one of the medicines you talked about what are some of the characteristics of the new GLP1 receptor agonist?

[C]

So Albiglutide is a once weekly solution that is of a GLP1 receptor agonist that is delivered once weekly. So, as you know, GLP1 receptor agonists have an effect working through one of the hormonal systems where the gut usually makes GLP1. This has the ability to raise the levels to really more than physiologic levels we call pharmacologic levels, so as to maximize its effect on helping the pancreas secrete insulin, suppressing glucagon and suppressing appetite, so that weight gain is not a complication of this therapy. Also, hypoglycemia is not a risk as long as patients aren't on insulin or sulfonylureas as background therapy. The advantage of giving a medication once weekly is obvious. One of the issues is convenience and the other is once weekly medications, because they tend to rise and reach their steady state very slowly, are better tolerated. They have fewer gastrointestinal side effects. So this medication is found to be approximately equivalent to axenatide bid at A1C lowering when it was studied head to head, perhaps not quite as efficacious as liraglutide. Again studied head to head, it is very well tolerated, has better GI tolerability than either of the medications and perhaps isn't associated with quite as much weight loss. I think that the decision on that or evaluation on that is still out, we're not exactly sure, but it is something that will be, I think, a welcome addition to what is becoming a very crowded field of GLP1 receptor agonists.

[B]

Those characteristics seem exciting and particularly the effect hopefully on adherence with the once weekly GLP1 is something I think we're all looking forward to exploring more.

[C]

Can you talk to us now about.

[B]

The SGLT2 inhibitor class of medications?

[C]

So the first SGLT2 inhibitor was released approximately April of 2013. This is a unique class of medications which works in the level of the kidney tubule. It blocks the ability of glucose to to re enter the bloodstream once it's filtered by the kidneys into the tubule that eventually connects to the ureter and bladder. So what happens in this setting is glucose gets filtered, it can't be reabsorbed completely back into systemic circulation, so it goes out with the urine and that in turn results in a significant lowering in blood sugars. So this class of drug is something that unlike almost anything else we have short of insulin, you can use at virtually any stage of the disease, because it doesn't require that the person have insulin in order for it to work. So it can be used early in the course of the disease or even added on top of insulin in patients who aren't achieving good glycemic control with that, it's generally very well tolerated. Although there is about a 10% incidence of vaginal yeast infections in women, lower incidence in men. There are some issues, especially as you get started on the medication, with having more frequent urination. As you can imagine, I always like to tell patients they can't pee out sugar cubes, so volume fluids goes with it. If patients are having any issues with lower blood pressure that can cause problems with dizziness. But in general, telling patients what to expect, telling them to drink plenty of fluid as you get started on the medication, has resulted in, at least in my experience, a very significant proportion of patients. Patients have been very successful at improving their glucose control. And again, since you're urinating out glucose, you're urinating out calories. And there's generally a modest weight loss associated with the medication as well. And again, no hypoglycemia unless it's on top of sulfonylurea and insulin.

[B]

Again, some pretty powerful characteristics. No hypoglycemia, weight loss, no weight gain associated with it. New classes or very attractive. Are there any Differences between the two medications in the SGLT2 inhibitor class of medicines?

[C]

Well, they've never been studied head to head, so you really can't make too much claim on differences of efficacy. There doesn't really appear to be all that much difference in terms of side effects percentage wise. In the clinical trials, slightly smaller percentage of patients on dapacliflozin experienced yeast infections compared to canagliflozin. They are, again, generally associated with the side effects we talked about. They're both associated with a very modest increase in LDL cholesterol and that appears to be a class effect on the medication for all the medications within that class.

[B]

And when would you use this class of medicines?

[C]

Well, I'm a big believer in allowing the patients to help participate in the decisions on what's important to them and the different options available. But I really put this right alongside the five class of drugs that were highlighted in the American Diabetes association recommendations for treatment of type 2 diabetes. So I just go through the options, including SGLT2, and give real short bullet points on pros and cons of each medication, again highlighting differences in cost. So patients can take that into consideration as well. And it has Been my general experience that patients will opt for the meds that don't cause weight gain and don't cause hypoglycemia. And they tend to gravitate towards the SGLT2 inhibitors because the fact that they're oral and the fact that there's some modest weight loss associated with them in most cases. So they enjoy the possibility of having a medication that's going to be easy to take. And I've had extremely small number of people who stop the medication for side effects.

[B]

That's helpful, it seems attractive and that's helpful to see where it fits in. How about the new inhaled insulin that was I guess recently approved in the FDA advisory panel? Can you update us on what we can expect with that?

[C]

So the technosphere inhaled insulin is a new engineered insulin that unlike the previous version of inhaled insulin, are monomers instead of being hexamers, which is how insulin generally exists in the vial as well as in the previous inhaled insulin. And the advantage of that is that first of all you've got a much smaller particle that's being inhaled and therefore it's easier for it to get into the systemic circulation secondarily because it doesn't have to be broken down. Once it reaches the systemic circulation, it has a very rapid activity. So the tetanusphere insulin most likely would be utilized in patients with both type 1 and type 2 diabetes who require prandial insulin control. So it's not going to give us a basal insulin. Most patients are probably going to need have a basal insulin to start with. But this would be instead of carrying a pen and giving an insulin injection before they eat, they would carry this palm sized or finger sized device that would have the insulin in it and they would just take an inhalation of insulin before they sit down to have their meal.

[B]

So it'll potentially could be used in place of rapid acting insulins that are now given by injection and presumably to make it easier for patients who are unable to be controlled on basal insulin to go to that next step in terms of Prandtl insulin control.

[C]

Right. Convenience and the whole issue related to the injection and doing that in public compared to taking a puff on something maybe a little more socially acceptable for some people. The other really important aspect is that it appears, although there are a few patients will have cough, it appears that the concern about pulmonary toxicity as was seen with the previous inhaled insulin seems to be much less as well. So the safety profile looks good with this new product.

[B]

Thanks so much. Two more questions. One, we've heard off and on about potential pancreatic risks associated with the incretin therapy. How do you communicate that issue with patients?

[C]

Well, the first thing I'd like to point out to patients is that the FDA database from which these concerns have arisen is an imbalanced mechanism for trying to evaluate safety of medications. So if a provider has an episode of a significant condition that occurs in a patient who's on a new medication, they are much more likely to report that than if that same physician has that same condition appear on something that's an old medication, like, for instance, sulfonylurea. So you end up having reports favoring newer medications so that you can't really do a good job of comparing relative risk between the older drugs and the newer drugs. So I explained to them that it's an imbalance, and I just use that really quick phraseology. And then I say, they've done multiple studies where they've looked at large databases and compared sulfonylureas to these new incretin therapies, and they have not been able to demonstrate an excess risk. That usually is enough. I tell patients the symptoms of pancreatitis and certainly tell them to get medical attention if they develop any. But I just reassure them using these medications for now, over 12 years, including the clinical trial experience I've had, I've not seen any cases of pancreatitis happen related to the medication. So I provide them with that. I can't be 100% sure, but I'm very comfortable with the safety of the medications, and that's usually enough. Now, I've had occasional patients who says, no, I don't want to take it because I'm just too worried about it, and that's fine. You have to move on and then say, okay, here's some other options for you. Again, having patients choose the medications they're interested in when I give them the option kind of takes some of that concern away because they're kind of choosing something I can then talk about safety, answer their questions related to it, and they're generally very comfortable with it when they leave the office.

[B]

It's interesting. As you're talking, it strikes me that one of the themes emerging in a number of the talks that we're hearing on this podcast is that issue of giving patients choices and individualizing therapy. And in doing so, patients are much more better and are more comfortable with the treatment they received. And we continue to keep hearing about that.

[C]

Yeah. So there is some early data suggesting that there's some improvement in adherence and satisfaction with their treatment. But I take it one step further. You know, I tell patients, you know, obviously I've just told you there's six different options that we can do at this point. So if this doesn't work for you, for one, whatever reason, please call us right away so we can kind of talk about what next. Because way too often that patients will go on something, have side effects, and I don't hear about it for three months. And then, of course, we've lost three months in our attempt to get their blood sugars down. So I think them hearing that there are other options helps to have them feel more comfortable that they have other choices and that we can move on more quickly. So I think it also helps just to have them understand. Yeah, yeah.

[B]

And then the last question I have is, how do you communicate any potential risks associated with the SGLT2 inhibitors?

[C]

So we talked about the side effects being primarily related to vaginal yeast infections in women. So, you know, I certainly talked to them about that risk only. Of the 10% of women that were reported in this mechanical flows in studies, three fourths of them or more just had one episode. And so I explained that to them and explained to how they can perhaps improve their genital hygiene to decrease the exposure of their vaginal tissue to potentially glucose that's from the urine. And then as far as the potential volume depletion, I reevaluate, I look at their blood pressure. If they're in the lower part of the range of what I think is appropriate for their patient, I might withdraw one or more of their medications. And if they're on a diuretic, oftentimes hold that, and then just really emphasize the importance of them drinking plenty of fluids, particularly as they get started and their blood sugar is dropping rapidly and they're urinating a lot of glucose in urine, that they can mitigate the potential volume depletion by just keeping themselves well hydrated. And that's really about all it takes. If they're on insulin or sulfonylnureas, I usually cut their doses down if their A1C is less than 8% or less than 1% above their goal. If they're more than 1% above their goal, I usually cut the doses back significantly, maybe not completely off, but decrease it to maybe the starting dose of sulfonylurea so that we can minimize hypoglycemia. Because this medication works the day they take it. I mean, they can see the impact on their blood sugars if they're doing them that day. They can tell that they're lowered immediately. It works that fast?

[B]

Well, that's an important thing. I'm glad that you mentioned and I'm sure that many of us listening don't know that. Well, this was incredibly helpful. I think this area of new medicines is critical for primary care. Talking about the new, once weekly GLP1 receptor agonist, a class of drugs that's really very new, the SGLT2 inhibitors and inhaled insulin, which hasn't even come out yet, but now we know more, more about has really been helpful for all of us. Carol, thank you so much.

[C]

My pleasure, Neil.

[A]

That concludes this special edition of Diabetes Core Update. On the next installment from the diabetes primary meeting this past June, we will hear Dr. Charles Schaefer discussing screening for and prevention of diabetes and Melanie Mabry discuss diabetes survival skills.