Diabetes Treatment Guidelines 2019

Long time coming…


but I’m back. Will try using this site as place to collect clinical pearls and educational resources from around the internets. Up first- Diabetes.

There are many new treatments for DM, and I can’t keep the initials straight, so first up, my round-up of DM treatments.

Metformin- first line therapy along with lifestyle modification.

GLP-1 RA: end in “glutide”. These are all injectable, some now once weekly. Some have proven CVD reduction benefits. In order of CVD benefit: Liraglutide (Victoza/Saxenda), Semaglutide (Ozempic), Exanatide (Byetta/Byderon).

SGLT2i: end in “gliflozin” These also have been shown to reduce CVD events, along with heart failure and progression of CKD. Empagliflozin (Jardiance) and Canagliflozin (Invokana) are examples.

DPP-4i: “Gliptins” Work by increasing Incretin, which helps the body make insulin when needed, and decreases glucose creation in the liver. Sitagliptin (Januvia) and Saxagliptin (Onglyza) are examples.

 

These are the most updated Standards of Care in DM, published Jan 2019. Here are the AACE executive summary and slide decks. 

I am teaching about treatment of DM, so here are some of the most relevant figures. Smart people have also told me that there is a great app with these algorithms. Search AACE Type 2 Diabetes.

First and Second line Treatments

Adding Injectable Medicines

And because conflict is interesting, here are the ACP guidelines for DM published last year, which set off a bit of a firestorm between Internists and Endocrinologists. The main differences have to do with treatment targets. ACP recommends aiming for HbA1c between 7-8% for most patients, and even higher for patients with less than 10 years life expectancy, nursing home patients, or with other chronic diseases. They feel we should focus on limiting harms and avoiding hypoglycemia in this population.   The ADA suggests keeping HbA1c less than 7% for most patients, with tighter targets for healthier patients who are doing well with current treatment, or those with cardiovascular disease. They are OK with higher HbA1c targets (<8%) in those who have demonstrated hypoglycemia, limited life expectancy, or comorbidities.

Enjoy!!

Advertisements

New Year, New You!

newyearsresolutions

So, I have conversations about diet, exercise and weight loss every day in my practice. But it seems that sometime around Jan 1, those conversations are more often started by my patients.  We are moving from the indulgent end of the year holiday season, to the fresh start of a new year.  So it seems natural to try to start fresh- live healthier, better, richer…

Well, maybe not richer. But there are a lot of people getting richer of our desires to look and feel healthier. So there are a lot of theories about how we got her, and promises to do this one thing, cut out this, take this pill, and turn your life around. Face it, a quick fix seems pretty damn appealing to all of us.  And I am in the pill pushing business. A big part of my job is to prescribe medicines.  So with all of these conversations about losing weight, medicine is a frequent question.

bann1

So today, I’m going to build on a recent morning report lecture on obesity to focus on medical treatments for obesity.  We’ll talk about old, new, tried and true and up and coming.  I’ll try to highlight the evidence base for these so that you can discuss in an informed way with your patients.

I also want to start with a disclosure.. I almost never prescribe medicine for weight loss. My bias (and I’ll argue, the evidence) is that these are generally not that helpful, and almost always patients gain back weight, plus more, once they stop taking them.  The studies that got these medicines approved were always coupled with a solid diet and exercise plan, and I think that most of the weight loss comes from that activity, NOT from the medicine.

peptobismol3Orlistat

Orlistat inhibits pancreatic lipases, so less fat is absorbed in digestion. In studies, patients on orlistat lost 5-10kg (compared to 3-6kg with diet/exercise alone). It also has been shown to lower blood pressure, and LDL levels more than would be expected by the weight loss alone.  It is safe, as most of it remains un-absorbed. However, the main side effects are GI related: bloating, nausea, and diarrhea. These are generally pretty limiting, and I haven’t found many patients willing to even try orlistat after hearing these effects. However, if patients can stick to a low-fat diet, the effects can be minimized.

 

Phentermine

Phentermine is a stimulant that suppresses appetite. It is the oldest of the approved medicines for weight loss, and also one of the cheapest. It is approved for 12 weeks of therapy, so most studies are of short duration only.  Studies show around 7kg of weight loss. Side effects include hypertension, tachycardia, anxiety, insomnia- in my experience these are pretty limiting.

There is a new medicine that combines phentermine with topiramate, Qsymia. The phentermine dose is lower than if prescribed separately, and it is approved for longer term use.  The initial trial for this Rx showed patients lost 8-10 kg in the first year, and could maintain weight loss if they continued for another year. Only about 60% of patients took the Rx for the whole first year.

Topiramate

So what about just Topiramate itself? Currently topiramate is approved for treatment of epilepsy and migraine. Using it for weight loss is off label- so beware. However, it has been studied, and patients lost about 4kg over 6 months in the various trials.

Lorcaserin

Lorcaserin (Belviq) is a serotonin receptor agonist, and thus serves as an appetite suppressant. A few other serotonin agonists have been tried over the years- fenfluramine- and lead to cardiac valve disease. Lorcaserin is more specific to the 2C receptor, which should minimize cardiovascular effect. In trials, more patients on lorcaserin lost at least 5% of their body weight (mean 5kg). There were also decreases in BP, HR, LDL, CRP, and glucose. All of the trials had dropout rates close to 50%.  Side effects include headache, nausea, URI sx, and back pain.

 

Diabetes Drugs: 

Liraglutide (Victoza, Saxenda- same Rx, two brand names) is the one drug in this group with an indication for weight loss. In patients without diabetes, trials showed around 7kg of weight loss, and in one trial, patients who lost weight pre medicine were more likely to maintain the weight loss if on liraglutide. Side effects include diabetesnausea/vomiting/diarrhea and rarely, pancreatitis.

Metformin Old drug, lots of data on weight loss, but still no indication for obesity treatment. Why? Patients don’t tend to lose a lot of weight with metformin- about 2kg.  But what different with metformin, is that there is long-term data that showed that patients could maintain that weight loss as long as they stayed on the Rx.  And it decreases incidence of diabetes in these people as well. Certainly something to consider in obese patients with pre-diabetes or otherwise at high risk.

Bupropion

Another off label use here, but post marking data did show a tendency toward weight loss in patients on bupropion. Remember, this drug increases norepinephrine effect, so likely has some sympathomimetic benefits. In one short (6 month) trial, patients on bupropion lost 7-10% of their body weight (compared to 5% lost on placebo).

There is a brand new combo drug that uses Naltrexone and Bupropion (Contrave). Patients got about 5% weight loss over a longer study (56 weeks), but only about half of the patients were able to complete the study. Nausea, headache, and constipation were common side effects. There is also a cardiovascular concern that is being actively monitored in the post-marketing period.

1345888562098_4352476

Big Picture

Diet and exercise are the key- slow and steady wins the race. There may be some small incremental gains with the medicines above, but I think that the evidence is thin, there are clear side effects, and the risks are not always understood. Given the millions of Americans that could end up on these medicines, I’d prefer to hang back and wait for the fallout before becoming an early prescriber of any of these.

Managing Sexual Assualt in Primary Care

Thanks to those who participated in a great discussion in AMR last week. I wanted to share some of what we talked about here…

Sexual assault is an unusal complaint inside of a primary care clinic.  Many victims head straight for the ER or a Rape Crisis Center, others never report their attack. But for many, their primary care doctor may seem like a trusted source for health care in a very scary and chaotic situation. Since it is also a scary and chaotic situation for the provider, I thought that an organized process may help you know what to do in such a scenario.


Legal Issues

The patient may need or want an exam in order to collect evidence for future charges against an attacker. There is a very specialized process that is used to collect evidence, and maintain the chain of custody.  I would recommend that you contact your Emergency Dept or Rape Crisis Center for help.  In Birmingham, the Crisis Center offers Sexual Assault Nurse Examiner (SANE) Exams in a safe and secure facility, and may be a more comfortable alternative to an ED.  They have a SANE nurse on call 24/7. Many times, this exam must be done within 72 hours of the attack.

Pregnancy Prevention

Most women should be offered post-coital contraception after a sexual assault.  The most effective oral option is Le
vonorgestrel, (Plan B is one brand name).  Ulipristal (Ella) is a newer form of emergency contraception that is effective up to 120 hours after unprotected sex.

 

STI Prevention

The CDC recommends antibiotic prophylaxis for GC, Chlamydia, and Trichomonas.  If your patient declines, you should see her back in a week for testing.  You need to give (all single dose therapies):

  • Ceftriaxone 250mg IM for Gonorrhea
  • Azithromycin 1g PO for Chlamydia
  • Metronidazole 2g PO for Trichomonas

Hepatitis B Prevention

If the Hepatitis B status of the attacker is not known, and the victim is not already immune, the victim should receive the Hepatitis B vaccine on first visit, and then at 1 and 6 months.  If the attacker has Hepatitis B, then you should offer HBIG.

HIV Prevention

There is some data that post-exposure prophylaxis with antiretroviral drugs prevents HIV transmission. Most of this data is in the healthcare setting, when folks like us are exposed with needles. The studies done in sexual exposure and IV drug users are all small and observational. Side effects with these medicines are fairly common, and usually of the GI variety.

Given limited data, and relatively low risk of transmission for a single sexual exposure (0.1% for consensual vaginal intercourse and 2% for consensual anal intercourse- transmission rates with nonconsensual sex are likely to be higher), the CDC only recommends post exposure prophylaxis (PEP) if:

  • The assailant is known to be HIV positive
  • The victim presents within 72 hours
  • There was exposure OF: eye, mouth, vaginal, rectum, other mucus membrane or nonintact skin
  • WITH: semen, vaginal fluid, blood, rectal secretions, milk, or other bodily fluids that are known to transmit HIV.

However, they do give you an option to treat other patients on a case-by-case basis. Many experts recommend that PEP is offered to all victims of sexual assault that present in the first 72 hours and have a chance at HIV exposure.  If you were going to prescribe, it should start within 72 hours (the earlier the better), and continue for 4 weeks. Three drug combinations are usually used, the same as in occupational HIV PEP.

  • Tenofovir/emtricitabine 300/200 plus Dolutegravir 50mg once daily
  • Tenofovir/emtricitabine 300/200 plus Raltegravir 400mg twice daily

Psychologic Support

Probably the most important thing that you can do. Your patient came to use because you were trusted, available, and supportive. You need to continue to be those things. After an assault, many victims will struggle with nightmares, anorexia, guilt, anxiety, and PTSD.  As a primary care doctor, you can gently ask about these issues, and guide your patients to helpful therapies and supportive environments. Again, rely on your local resources for crisis counseling and psychiatry, in addition to using all of your own talents.

Here is a NEJM article (subscription needed) if you are interested in reading more: NEngl J Med 2011; 365:834-841.