Diabetes Core Update Special Edition - Diabetes is Primary 2015 Part 1

Summary

---

Diabetes Core Update Special Edition – Diabetes is Primary 2015 Part 1

Podcast by the American Diabetes Association
Released: June 10, 2015
Guests:

• Dr. Andrew Reinhart (Chief Medical Officer, Glytech)
• Dr. John Buse (Professor of Medicine, University of North Carolina at Chapel Hill)
• Hosts: Dr. Neil Skolnik, Dr. John J. Russell

---

Overview

This special edition episode of Diabetes Core Update covers highlights from the 2015 “Diabetes is Primary” Conference, part of the American Diabetes Association’s Scientific Sessions. The episode focuses on:

• Updates to the ADA Standards of Care (Dr. Andrew Reinhart)
• New medications in diabetes, particularly SGLT2 inhibitors and insulin formulations (Dr. John Buse)

These segments are designed to bring practicing clinicians up-to-speed on important changes impacting diagnosis, screening, medication choices, and diabetes management.

---

1. Updates to the ADA Standards of Care

Speaker: Dr. Andrew Reinhart
Timestamps: [02:14]–[09:08]

Key Discussion Points

• BMI Cutoff for Diabetes Screening ([02:22])

  • New Asian BMI threshold for screening is 23 (previously 25 for all populations).
  • "Anybody that you have that is overweight, obese, meets these criteria and is at high risk for other reasons... those are the types of people we want to be screening." — Dr. Reinhart [02:36]

• Physical Activity Recommendations

  • Encourage patients to stand or move every 90 minutes during the day, not just remain seated for hours.
  • “I love my new Apple watch because it reminds me to get up every hour. And the standard is saying ... at least standing or moving every 90 minutes throughout the day.” — Dr. Reinhart [02:50]

• E-cigarettes

  • No strong evidence to support their use; not recommended in the guidelines.

• Immunizations

  • Now mirrors CDC guidance on pneumococcal vaccines (PCV13 and PPSV23); not a significant change, but ensures alignment.
  • “The only change was mirroring what the CDC is saying in terms of that vaccination.” — Dr. Reinhart [03:18]

• Glycemic Targets ([03:31])

  • Pre-meal glucose range changed from 70–130 mg/dL to 80–130 mg/dL.
  • Postprandial target (<180 mg/dL at 1-2 hours) and A1C target (<7%) unchanged.
  • Emphasis on individualization of A1C target: depends on patient’s diabetes duration, complications, and comorbidities.
    • “Some folks less than six and a half may be appropriate, some people closer to eight may be appropriate.” — Dr. Reinhart [04:15]

• Medication Choices After Metformin ([04:32])

  • SGLT2 inhibitors added as a new sixth class to consider after metformin.
  • Guide to individualizing second agent: consider cost, efficacy, risk of hypoglycemia, side effects, and whether glucose issues are fasting or postprandial.

• Blood Pressure Targets ([05:18])

  • New systolic/diastolic target is less than 140/90 mmHg (previously 140/80).
  • Tighter control (<130/80) may be considered when attainable without undue burden.

• Statin Use Guidelines ([05:50])

  • Statin initiation now based on risk, not LDL alone; mirrors ACC/AHA guidance.
  • All adults 40+ with diabetes should be on a statin.
  • <40-year-olds with CVD: high-intensity statin; without CVD, rarely indicated.

• Foot Care Recommendations ([07:02])

  • At each visit: Examine feet of any patient with insensate foot, foot deformities, or history of ulcer — not just annually.
  • “If you have somebody high risk or had problems, ... you really want to check them every time.”

• Targets for Children and Adolescents

  • Uniform A1C target of <7.5% for all children/adolescents (previously age-stratified).
  • “Especially for our family practitioners and pediatricians... less than seven and a half is our target for all.” — Dr. Reinhart [08:22]

---

Memorable Quotes

• “I think it’s really important to look at those things as we add those second agents.” — Dr. Reinhart [04:58]
• “Those are the big changes regarding adults, the only one regarding adolescents and children...” — Dr. Reinhart [07:56]

---

2. New Medications in Diabetes

Speaker: Dr. John Buse
Timestamps: [09:33]–[20:08]

SGLT2 Inhibitors: Mechanism, Benefits, and Risks

• Mechanism of Action ([09:53])

  • Inhibits kidney reabsorption of glucose, leading to excretion in urine.
  • Results in weight loss and modest BP lowering due to calorie and sodium loss.
  • “Most of us over the age of 50 spent the bulk of our career trying to keep glucose out of the urine. And so putting it there on purpose is ... a bit different than what we're used to doing.” — Dr. Buse [10:27]

• Clinical Efficacy

  • As effective as metformin, sulfonylureas, and DPP-4 inhibitors.
  • Additive effects when combined with other classes.

• Common Side Effects ([11:17])

  • Increased risk of genital mycotic infections: 10–20% of patients may have ≥1 episode; typically responds to OTC treatments.
  • "Probably somewhere on the order of 10 to 20% of patients having one or more episodes, probably near the lower end." — Dr. Buse [11:40]
  • Urinary tract infection risk is not clearly increased.
  • Some risk of dehydration; diuretics may be stopped when starting SGLT2i.

• Serious but Rare Side Effect: Euglycemic DKA ([12:37])

  • FDA warning: can occur without significant hyperglycemia.
  • Patients on SGLT2i who are unwell should have urine ketones checked.
  • “The absolutely critical thing to remember is ... particularly if they're on an SGLT2 inhibitor ... you should check urine ketone to make sure they don't have this euglycemic diabetic ketoacidosis.” — Dr. Buse [13:43]

• Use with Insulin ([15:33])

  • SGLT2 inhibitors can be used with insulin.
  • In insulin-requiring type 2 DM, addition of SGLT2i led to reductions in A1C, weight, and BP.

---

New Insulin Formulations

• Insulin Glargine U300 ([16:58])

  • More concentrated, allowing higher insulin doses per injection.
  • Longer duration of action, more stable profile, modest reduction in hypoglycemia.
  • Switches from U100 may require titration as U300 is a bit less potent.

• Biosimilar Insulin

  • First biosimilar glargine in the US; pending resolution of legal hurdles.

• Insulin Degludec

  • Structurally distinct, very long half-life, stable action, lower risk of hypoglycemia.
  • Several new options set to change insulin landscape in the next 6 months.

---

Memorable Quotes

• “It does make sense ... in at least one study of a rather dramatic effect of SGLT2 inhibitors. That is a great overview.” — Dr. Buse [15:53]
• “It is complicated these days to keep track of 13 different classes of diabetes drugs ... just an onslaught of information in the primary care community.” — Dr. Buse [20:08]

---

Timestamps & Segments

• [00:03–02:14] - Episode introduction & overview of all “Diabetes is Primary” segments
• [02:14–09:08] - Dr. Andrew Reinhart: ADA Standards of Care updates
• [09:33–20:08] - Dr. John Buse: New diabetes medications and insulins

---

Summary Takeaways for Clinical Practice

• Stay up-to-date on annual ADA Standards of Care—significant changes affect screening, glycemic and blood pressure targets, statin use, and foot care protocols.
• Screen Asian patients at lower BMIs (≥23).
• Emphasize frequent movement for patients to reduce sedentary time.
• SGLT2 inhibitors are now a standard second-line agent with benefits on weight and BP, but carry risks of mycotic infections and rare DKA.
• New insulins (U300, Degludec) and biosimilars will provide more treatment options—learn their unique dosing and safety profiles.
• Individualize treatment based on risk, comorbidities, and patient factors—especially when aiming for A1C and BP targets.

---

For more, including the full lectures:
Visit professional.diabetes.org/ce for webinars and additional resources.

---

Transcript

[A]

Hello, I'm Dr. Neal Skolnick and I'd like to welcome you to this special edition of Diabetes Corps Update. On this special series of podcasts, we will be interviewing faculty who presented during the American Diabetes Association's Scientific Sessions Diabetes is Primary Conference on June 6, 2015. In part one of the Diabetes Primary Podcasts, we will cover Dr. Andrew Reinhart's discussion and update of the standards of care. And then we'll talk to Dr. John Buesse who discussed new medications for diabetes. In Part two of our Diabetes is Primary special series of Diabetes Core Update that will come out mid July, we will hear Dr. Charles Schaefer discussing what to do after basal insulin is no longer sufficient and then talk to Dr. Jim Chamberlain about his talk hypoglycemia. In part three of our diabetes is Primary special edition of Diabetes Core Update, which will come out mid August, we will hear Dr. Jay Shubrook discuss atypical diabetes, Dr. Henry Rodriguez discuss diabetes in adolescence, and Dr. Eric Johnson discuss a wonderful talk on continuous glucose monitoring and insulin pump therapy for primary care. For more details and in fact for the full talks of the Diabetes is Primary lecture series done at the Scientific Sessions 2015 of the American Diabetes association, please visit www.professional.diabetes.org ce to access the webcasts of these lect. Our Next speaker is Dr. Andrew Reinhardt.

[B]

Who is the Chief Medical Officer for Glytech, who discussed the changes in the Standards of care. An update for our audience.

[A]

Dr. Reinhart, welcome.

[C]

Thank you for having me.

[A]

If you can give us just the highlights of your talk for our audience.

[C]

Okay, well that's what I'll have to do. I actually went over the entire standards, which is about a two hour lecture we've got in 45 minutes. But to highlight the actual changes from last year's standards, the first one is in terms of the BMI cutoff for screening for folks for type 2 diabetes. And the big change was a bmi less than 25. But for Asians a BMI cutoff of 23 as a new screening criteria for for once again screening for type 2 diabetes. So anybody that you have that is overweight, obese, meets these criteria and is at high risk for other reasons. They may have high ethnic risk factors, they may have physical activity, is low, have a history of low HDL, have a history of high triglycerides, etc. Those are the types of people people we want to be screening. But that cutoff for Asian BMI is what changed to 23 and then certainly in terms of activity A big change is get up and what we mean by that. I said I love my new Apple watch because it's telling me it reminds me to get up every hour. And the standard is saying make sure people are up and at least standing or moving every 90 minutes throughout the day. So you don't want to just be sitting there for hours upon end at your desk or with other activity or in a car. If you're a truck driver off the side of the road, get up and move a little bit. Not big fans of E cigarettes. There's no great data showing that they're very helpful. Is another change in the standard and surrounding immunizations. There was a change and basically the change was just to mirror the current CDC guidelines for prevention regarding the pneumococcal vaccine 13 and 23 in older adults. So really the only change was mirroring what the CDC is saying in terms of that vaccination. So not a big change there. There was a change regarding glycemic targets, which I think is interesting. For years we talk about the 70 to 130 target. The ADA has pushed for pre meal targets and they've changed that target from 70 to 130 to 80 to 130 to more closely match what those averages probably mean in terms of A1C. The postprandial target of less than 180. Peak 1 to 2 hour post meal has not changed and the A1C target has not changed. But I don't think it's important to stress the individualization of that ADA target of less than 7. So less than 7 is a general target. This hasn't changed, but I think I'd just like to stress it. And so we really want to individualize that target based on a patient's how long they've had diabetes, their complications, whether they have cardiovascular disease, socioeconomic issues that they may be dealing with. So some folks less than six and a half may be appropriate, some people closer to eight may be appropriate. But what actually changed in the guideline was the pre meal 80 to 130 is now the target in terms of the treatment output position statement. It didn't necessarily change except they added the SGLT2 inhibitor class as one of those five now six classes of medications we can add after metformin. And so that is another change. And I'd like to highlight too, as we do choose that second agent. The idiot does a very great job of what do we need to look at as we do that. So let's look at cost, let's look at efficacy. Let's look at hypoglycemia risk. We'll also look at side effects as and I'm just absolutely blanked on the 5th. And then we also want to, I like to add on to look at whether you're having a fasting or postprandial issue. So I think it's really important to look at those things as we add those second agents. Now the other big changes revolve around the cardiovascular disease. So the first change is blood pressure target. So we move from a 140 over 80 target to 140 over 90 or less target for blood pressure. However, if you can get to that 130 over 80 easily without undue treatment burden, you may want to try to get folks there. But the big change was making that systolic change from 80 to 90. And this is all evidence based. The other big change is around statin therapy. And really basically what the ADA has decided is, hey, we're going to kind of mirror and go more towards the cardiology, the ACC American Heart association guidelines. And that is initiating statin therapy regardless of ldl, more related to risk and using moderate and high intensity statins. Anybody 40 and over should be on a statin. Anybody younger than 40 that has cardiovascular disease needs a high intensity statin. At high risk for cardiovascular disease needs a moderate dose statin or moderate intensity statin. And the only group of people not to be on statin therapy are folks younger than 40 with no cardiovascular risk factors, which are very few folks with type 2 diabetes. Another addition to the guidelines or a change was really surrounding microvascular complications and foot care. And basically what the guideline says now is that all patients with an insensate foot or a loss of protective, loss of protective sensation have foot deformities or a history of a foot ulcer. You really want to examine their feet at every visit and not just once a year or not those it at all. So everybody we want to. If I have patients with no risk of foot problems and have never had any, a yearly exam is fine. But what they're saying now in the guideline is if you have somebody high risk or had problems, had ulcers, they've got a big bunion or have had calluses in the past, have hammer toes or insensate, you really want to check them every time they're in, just tell them, hey, go ahead and take those shoes and socks off after the nurse gets them in the room. So those are the big changes regarding adults, the only one regarding adolescents and children There used to be a slow increase or decrease over time for adolescents and children in terms of their A1C target. So real young kids less than 8 and a half and then 8 7.5. Now it's just 7.5 across the board for adolescents and children. So I think that's important to talk about as well because especially for our family practitioners and pediatricians out there that take care of younger kids. But less than seven and a half is our target for all this change.

[A]

Fantastic.

[B]

Dr. Reinhardt, that was a wonderful overview of the changes. It's really important to stay up every year with those changes. The Standards of Care, of course, are published every year in Diabetes Care in the January edition. Worth looking at. And a number of us have been working on disseminating a shortened version of the study, Standards of Care and other publications. Again, thank you so much for joining us.

[D]

We're now going to talk to John Buuse, who is a professor of medicine at the University of North Carolina in Chapel Hill. Dr. Buuse is talking about new medicines in diabetes. Welcome, Dr. Buuse.

[E]

Thank you very much.

[D]

What are the highlights of what we ought to know about the SGLT2 inhibitors?

[E]

Well, I think the most important thing is to recognize the mechanism of action because I think it does explain most of the adverse events. I think it's important to feel comfortable with the mechanism of action because it is a little shocking. So way back 30 years or so ago, a compound called Oritzin was developed and was practically a cure for diabetes in mice. And the way, the way that drug development happened, many people felt that drugs with this mechanism of action just didn't make a lot of sense. So there's a molecule called SGLT2, which in the kidney tubule brings sugar from the urinary space back into the plasma space. And these SGLT2 inhibitors block that molecule. And as a result, patients excrete urine through, I mean, excrete glucose through the urine 24 hours a day. Most of us over the age of 50 spent the bulk of our career trying to keep glucose out of the urine. And so putting it there on purpose is a bit, is a bit different than what we're used to doing. As you might imagine, losing glucose in the urine means a caloric loss. And so patients also have a tendency to lose weight. And this glucose transporter, there's a sodium exchange mechanism that helps pump the glucose across a gradient. So there's also a bit of sodium loss and as a result, some reduction in blood pressure. In the head to head studies against metformin and sulfonylureas and DPP4 inhibitors. They're as effective as any of the other oral agents. And because it's a completely novel mechanism, these SGLT2 inhibitors play well with other drugs. So virtually every combination that's been studied is additive in its effect. So it's really quite an exciting drug. Powerful glucose lowering, weight loss and blood pressure reduction on the side effect side, because you put glucose in the urine space. There's some of the genitourinary infectious issues that we see in uncontrolled diabetes, so namely vaginal yeast infections in women and balanitis in men, particularly uncircumcised men. The rates vary by study, but I think it depends on how closely you question patients about these occurrences. But probably somewhere on the order of 10 to 20% of patients having one or more episodes, probably near the lower end, usually responds very well to typical over the counter medications. Only about a third of people who have one episode will have a second episode and only about a third of those people will have a third episode. So we're talking around 1% or so of patients who really end up quite bothered by this sort of genital yeast infections. The urinary tract infections is more controversial. Not really clear that that is actually an adverse consequence of these drugs. And then some patients have dehydration. We usually stop diuretics when we start the SGLT2 inhibitors. And there are trivial changes in lipids that really aren't worth talking about. And then the last thing that I'll mention is there's very recently a warning that patients can develop diabetic ketoacidosis without substantial hyperglycemia. So we call this euglycemic diabetic ketoacidosis. It's very rare in type 2 diabetes. It may not be so rare in the off label use of these SGLT2 inhibitors in type 1 diabetes. I think the absolutely critical thing to remember is if you have a patient with diabetes in general, but particularly if they're on an SGLT2 inhibitor where absent insulin, the glucose will still be lowered and they feel unwell, you should check urine ketone to make sure they don't have this euglycemic diabetic ketoacidosis, which in the beginning could just be a syndrome of nausea and malaise with a glucose of 100 or 200 in the setting of SGLT2 inhibitor therapy.

[D]

I'm glad you mentioned that because that warning just came out last week and I think it's been confusing for a lot of people. Can you mention just for a minute about the use of SGLT2s with insulin? Is that a reasonable use or is that something that doesn't make sense?

[E]

Yeah, no, again, it does make sense and there are some studies that have been completed. The most interesting of which, if I get the. If I remember the details, were patients who start out in the study on about 70 units of insulin with an A1C around 8, 8 and a half. So rather typical patients with type 2 diabetes kind of failing insulin therapy, and they added the SGLT2 inhibitor and they had a substantial reduction in A1C on the order of 1, 1.5% with weight loss and blood pressure reduction, as compared to continuing to titrate the insulin. So there's good evidence in this sort of toughest population of patients that we manage in diabetes, in at least one study of a rather dramatic effect of SGLT2 inhibitors. That is a great overview.

[D]

They really are a very versatile group of medicines, useful with a lot of different medicines and side effects to be aware of, but usually well tolerated. And then, Dr. Busey, you said you were also going to talk a little bit about some new insulins that are coming out.

[E]

Right. So, very recently, a novel formulation of insulin, glargine, called U300. So it's sort of a concentrated glargine. In the future, it will allow us to deliver higher doses of insulin in a pen, in one injection. But for now the dose is capped in the pen, similar to the currently available formulations. But the result of this more concentrated insulin is a somewhat longer duration of action and somewhat greater stability day to day as far as the release profile into the circulation of insulin, and as a result, modestly improved rates of hypoglycemia. The only issue to be aware of with this U300 formulation is that it's not quite as potent. They probably got the dosing just a little bit off. And as a result, if you were to switch a patient from glargine in the current U100 to the U300 dose, you know, the recommendation would be to generally end up with a dose equivalent number of units and then to continue to titrate to get the fasting glucose lower, because at the end of the day you'll very likely require more of the U300. And then there's a lawsuit about the biosimilar insulin, which is fundamentally glargine insulin being produced by another manufacturer. This is the first of the biosimilars in the US and the legal pathway requires this lawsuit. To be able to get the drug on the market. I don't know when that is likely to happen, but it is likely to happen in the very near future. And then there's another form of insulin called insulin Deglodex, which is again, a longer lasting formulation of insulin. This one's structurally different from Glargine, but with a very, very long half life. Again, the concept being the longer the half life, the more stable the, the profile, the less hypoglycemia, less glycemic variability day to day. And so there'll be a lot of change in the next six months or so in the insulin marketplace.

[D]

Well, that's really helpful and it's something that's helpful for us as primary care to be aware of as it's emerging because it can become very confusing very quickly if you're not keeping up. Dr. Busa, thank you so much. Thank you so much for going over your lecture for our listeners. I just want to say how much we appreciate that.

[E]

Well, thank you very much. It is complicated these days to keep track of 13 different classes of diabetes drugs, many of them being marketed by more than one company. And it's just an onslaught of information in the primary care community regarding diabetes, making it quite a challenge these days.

[A]

So that wraps up part one of our Diabetes is Primary podcast, recorded at the 2015American Diabetes Association Scientific Sessions. In part two, we will be hearing Dr. Charles Schaefer discussing what to do after basal insulin is no longer sufficient and Dr. Jim Chamberlain discussing data on the importance of and management of hypoglycemia. Part two will be released mid July. And then in part three of this series, we will hear Dr. Jay Shubrook discussing atypical diabetes and Dr. Henry Rodriguez discussing diabetes in adolescents and Dr. Eric Johnson discussing continuous glucose monitoring and insulin pump therapy for primary care. And that will be released early to mid August. For more information and in fact, for the complete lectures in this series in webinar form, just go to www.professional.diabetes.org ce to access the webinars of these lectures. Thank.

[E]

You.

[C]

It.