Possibilities today...Treatments Tomorrow

- NORCAL MEDICAL RESEARCH -

NOVEMBER/DECEMBER 2024 NEWSLETTER

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Welcome to the November/December NorCal Medical Research Newsletter!

As this month is all about giving thanks, I’d like to express my sincere gratitude to our readers, the generous participants in our clinical studies and the doctors and friends who refer patients to us. Participation in a research study right here in Marin might bring an opportunity to focus on one’s health in a new way, to improve health or to help the development of a drug that could benefit others worldwide in the future.

Presently, we are very excited about our newest GLP-1 weight loss studies for persons with AND without diabetes, both studies currently enrolling. We are also still seeking patients with hypothyroidism for a Thyroid Study which compares animal derived thyroid supplement, Armour (T3/T4), to synthetic thyroid hormone, levothyroxine (T4), as replacement therapy treatment. See below and visit our website for more details on all three studies.

I hope you enjoy the article I wrote this month titled GLP-1 Medicines in 2025: The Importance of Clinical Trials which you can read in our NorCal Knowledge Nuggets section below. It reviews how GLP-1 medications were developed over the past three decades (YES, they have been around for that long!!!) through meticulous research and clinical trials and summarizes what we know and what we still want to learn from upcoming clinical studies, just like the ones we are conducting right now.

I also briefly discuss the compounded drugs and their safety and efficacy, a topic which is quite confusing to many patients who are considering taking weight loss drugs. Only FDA-approved medications may be used in our clinical trials. Compounded drugs are never used in our studies.

While drugs like Ozempic and Mounjaro have been very successful in yielding never before seen weight loss for many people, manufacturers like Eli Lilly, Novo Nordisk and new companies as well, continue to work to develop and test new drugs through clinical trials using novel GLP-1 RAs and combinations of the existing GLP-1 RA drugs with other new receptor agonists in order to maximize weight loss benefits and minimize side effects. They are also testing new oral drugs in this same class to reduce weight without injections, like our newest study enrolling now and others scheduled for 2025!!!

You can refer to our June newsletter for more information about the new weight loss medications.

Remember there is no cost to participants in our clinical trials for study medications, lab or clinical monitoring. (See our “What you Give, What You Get flyer”).

Because there’s so much interest in the new weight loss drugs, contact us immediately if you might be interested or have a friend or loved one who might be. Call us to get information about qualifying, to get screened or to get on a waiting list for the study that’s right for you while space is available.

We wish you all a Happy and Healthy Thanksgiving! Please refer to our November 2023 newsletter for some tips to take to your traditional banquet tables. These few delicious twists will increase fiber and the nutritional content of your feast and modulate simple sugars, refined carbs and saturated fats.

Get to know us better at NorCalMedicalResearch.com and contact us at 415-461-1585 or info@norcalmedicalresearch.com with any questions. Visit us and follow us on Facebook, LinkedIn and Nextdoor!

Thank you for supporting our mission to improve patient outcomes through careful data gathering and clinical research at our site right here in Marin!

In health,

Dr. G

Linda Gaudiani MD FACE FACP

Medical Director

Click here to get acquainted with our physicians

and here to meet the rest of our staff.

Dr. Linda Gaudiani

Dr. Elizabeth Lowe

Dr. Irene Teper

- STUDIES NOW ENROLLING -

NEW WEIGHT LOSS STUDY FOR PERSONS WITH TYPE 2 DIABETES

We are currently screening patients for this new weight loss study

which will test once weekly injectable weight loss medications as combinations of Tirzepatide (Mounjaro) and LAARA (Long-Acting Amylin Receptor Agonist) to assess changes in body weight compared to placebo (inactive drug) during treatment. The study will enroll persons with excess weight and type 2 diabetes.

90% of participants will receive active investigational drug, only 10% of patients will receive placebo.

You may be eligible to join this study if you:

are aged 18 to 75 years
have excess weight with a BMI of 27 or more
have been diagnosed with Type 2 Diabetes for at least 6 months
have an HbA1c of 7 to 10.5
are on either no diabetes meds or are on Metformin, with or without an SGLT2 inhibitor.

Please call if interested!

NEW WEIGHT LOSS STUDY FOR PERSONS WITHOUT DIABETES

We have started recruiting for another weight loss study for people without diabetes and this study drug is an oral, not an injectable weight loss medication!

The study will test a medication that is a daily pill to improve weight management in adults without diabetes who have obesity or overweight compared to placebo.

The study is 48-weeks in duration.

You may be eligible to participate if you:

are aged 18 to 75 years
have a BMI of 27 or more
do not have diabetes
have not taken part in a clinical research study for weight loss in the past year
are not of childbearing potential.

This study may fill quickly so call us for more details if you or a friend are interested.

THYROID STUDY

This Thyroid Study compares the use of purified naturally derived thyroid replacement therapy as Armour thyroid LT3/T4, to synthetic levothyroxine LT4. Armour is made from purified porcine thyroid and contains both T4 and T3 thyroid hormones.

The study compares dose equivalents of LT4 (levothyroxine) and Armour so that individuals can be safely converted from one to the other if needed. All participants will start on Armour thyroid and later will be randomized to receive either LT4 synthetic or Armour T3/T4. Thyroids levels will be monitored very closely and thyroid hormone replacement doses will be adjusted per protocol to keep thyroid levels optimal throughout the study and patients feeling their best.

You may be eligible to participate if you:

are 18 to 75 years of age
are diagnosed with primary hypothyroidism for at least one year
have had no thyroid surgery within past 12 months
have been on continuous thyroid replacement therapy with LT4 (levothyroxine) for the last 6 months
have had a normal TSH documented in the past year.

The duration of the study is one year.

As with all clinical studies, participants never have to pay for the study drugs, study visits, or for the procedures or tests that are needed as part of these studies. Remember all patients receive a small stipend for their time and may be reimbursed for approved, study-related travel. All information is shared with your own doctors as requested but is otherwise strictly confidential.

Please contact us at 415-461-1585 or info@norcalmedicalresearch.com with questions.

- NORCAL KNOWLEDGE NUGGETS -

THE GLP-1 MEDICINES IN 2025: THE IMPORTANCE OF CLINICAL TRIALS

When people ask me what I do these days and I tell them I continue to direct numerous clinical research studies in my field of expertise, they are sometimes surprised: “But you’re a lifelong physician!” I don’t blame them, as the critical mission of research trials is an area of medicine that’s not discussed much. Yet many, if not most of us, take medications as needed and prescribed, forgetting that each one of those drugs had to be studied for efficacy and safety before it could be made available for human use. Meticulous, real world clinical trials are the essential final step to confirm scientific hypotheses, early bench research and humane animal studies. Clinical trials are a critical step in bringing FDA approved, very useful and life-saving medications to all of us!

So, let’s talk about the tidal wave of interest in the GLP-1 medicines for instance and how NorCal has been, and is involved in the clinical trials of these weight loss “Wonder Drugs.” How did the GLP-1 drugs get to celebrity status and what’s next? What more do we need to know?

THE FIRST GLP-1 DRUGS FOR PERSONS WITH DIABETES IN 2005

A comprehensive review of the Safety and Efficacy of the GLP-1 medicines appeared in Diabetes Care this month which summarizes all the major clinical trial results that have brought us to our current state of knowledge about the GLP-1 medications. As an endocrinologist and clinical researcher here in Marin since the mid 1980’s, I was very involved in the early research trials and development of the first drug in the GLP-1 class, approved and introduced in 2005, as well as so many since!

The whole notion of “glucoregulatory” hormones produced in the gut was a revolutionary concept back then. The exciting discovery was that there were hormones in the gut, in addition to insulin from the pancreas, that were critically involved in metabolism and specifically the utilization of glucose as fuel. These hormones were excreted in response to signals around eating; when secreted by the gut they assisted the function of insulin in keeping glucose levels stable after a meal and helping glucose get from the gut into the cells of muscle, liver and other vital tissues. It was found that GLP-1 drugs that could occupy the receptors for these hormones, the naturally occurring GLP hormones, could mimic their activities and lower blood glucose in type 2 diabetes patients after meals by several different pathways. They had direct effects on reducing gastrointestinal motility, limiting stored glucose release from the liver, assisting in stimulating insulin from the pancreas and in the brain, they had effects on the appetite center.

Other drugs in this class began to emerge rapidly as decades of simultaneous clinical trial results confirmed the impressive efficacy and safety of the “incretins,” as the GLP-1 class was also called, in lowering HA1C in persons with type 2 diabetes. Longer-term clinical research studies in type 2 diabetes showed additional benefits including significant weight loss, major reductions of major adverse cardiovascular events (MACE) and kidney disease (24%), and all-cause mortality (12%)!

THE EMERGENCE OF THE MAJOR GLP-1 MEDS FOR PERSONS WITHOUT DIABETES

Further research was undertaken in people with overweight conditions and cardiovascular risks who did not have diabetes. Dosages were adjusted in further trials looking for optimal outcomes and safety. Even greater reductions in weight and adverse cardiovascular events were documented in persons without diabetes, leading to the emergence of the major GLP-1 meds we now have available to treat obesity and overweight conditions in both people with diabetes, most of whom are overweight, and also in persons without diabetes who were overweight and had cardiovascular risks.

The worldwide population that might benefit from these drugs is staggering and in general these medications have shown an excellent safety and risk profile. Without the crucial studies of many decades, we would not have the GLP-1 “Super Drugs” at all. Kudos to the thousands of researchers, doctors, medical workers and patients for pursuing this difficult but vital work!

We at NorCal Medical Research, formerly known as Marin Endocrine Care and Research, have participated in numerous weight management studies as well as GLP studies for over three decades and we are also participating in long-term clinical outcome studies on some of the already approved drugs in this class. We are very excited to be part of the emerging new GLP-1 and other similar drug trials to learn more and to improve options and availability for people with overweight, obesity and associated metabolic disorders.

WHAT DO WE STILL NEED TO KNOW THAT WE MIGHT FIND OUT FROM CLINICAL STUDIES?

How durable are the results and what will happen if people discontinue use after some time?
How about the results from combinations of GLP-1 meds with other glucoregulatory hormones that have since been discovered like GIPR, glucagon, amylin and others. Will they yield even better results? Will the side effects be reduced?
Can we develop safe and effective oral preparations?
What is the long-term safety profile of these preparations? Will they be found to have serious adverse events over time?
Can new formulations improve tolerability, especially reducing the gastrointestinal side effects that some 50% of people experience on these meds?
What about preservation of lean body mass and avoidance of muscle wasting (sarcopenia)?
Will this group of drugs be useful to treat other conditions, like addictions, neurologic diseases?
What about safety in other populations, children, adolescents, the elderly, hospitalized persons?
Are cheaper compounded products effective? Safe?

Lastly, it is hoped that an expanded choice of effective GLP-1 medications will drive the cost of these drugs down so that their full potential can be realized globally.

So, there’s a lot of work we must do carefully as a medical community, but our success depends on the generous participation of patients in these very meticulous, medically monitored clinical trials. (See our "What you Give and What you Get" poster).

Participants in well conducted clinical trials may benefit from the investigational product itself, as well as from the nutritional, exercise and lifestyle counselling that may be part of the protocol. No medical insurance is required, and personal identity and results are highly protected by codes. There is no cost at all to a participant in a clinical research study. Labs, medical visits, monitoring, and study drugs are free, and stipends are provided for patient travel and time. Protocols are very carefully explained to interested persons as well as the possibility of receiving placebo (inactive comparators) in some study protocols as part of Informed Consent procedures. Investigator physicians can communicate results and progress with primary care doctors as requested.

We’re very excited to be screening people now for two new GLP-1 type weight loss studies. Please visit our website for more information on participation.

GLP-1 MEDICATION SHORTAGE AND COMPOUNDED DRUGS

The recent surge in demand for GLP-1 medications has led to significant shortages and supply chain challenges. Although these medications have proven very effective in managing obesity and diabetes, both cost and scarcity have forced many patients to explore alternatives to FDA approved and physician prescribed products.

WHAT IS A COMPOUNDED DRUG?

According to the FDA (US Food and Drug Administration), a drug may be compounded for a patient who can’t be treated with an FDA-approved medication. For example, a patient who has an allergy to a certain ingredient and needs medication to be made without it or needs a medication that appears on the FDA Drug Shortage List, might look to a compounding pharmacy to provide a substitute.

The quality and safety of compounded medications can vary widely however, depending on the pharmacy's adherence to regulations and quality control standards. The efficacy and safety of compounded drugs have not been systematically studied. Therefore, there may be issues with purity, safety and efficacy and some problems have been reported.

It is no surprise that obesity medicine physicians typically advise their patients against taking compounded weight loss drugs. Practitioners want to provide the most effective and safe treatments for their patients and usually recommend treatments that have been rigorously studied in controlled clinical trials. Compounded medications have not been studied in large control trials and are not FDA approved.

So be careful: if you find you can get a medication without a prescription, without a medical exam or consultation, or if you are able to get it online from a spa, weight loss clinic or your local gym without medical supervision, it may be a red flag.

THE RISKS AND BENEFIT OF GLP-1 COMPOUNDED MEDICATIONS

Potential Benefits:
Access to medication during shortages
Customized formulations for specific patient needs
Lower price

Potential Risks:
Variability in quality and potency
Increased risk of contamination or adverse effects (with subcutaneous injections, any impurities from a non-sterile drug reach the bloodstream immediately)
Lack of FDA approval and oversight

IMPORTANT CONSIDERATIONS

Consult with a Healthcare Provider: Discuss the pros and cons of compounded medications with your doctor.
Choose a Reputable Pharmacy: Select a compounding pharmacy that is licensed and accredited.
Ask Questions: Inquire about the source of the active pharmaceutical ingredients, the manufacturing process, and quality control measures, including the protocols used for sterility and for chemical analysis.
Monitor for Side Effects: Be vigilant for any adverse reactions and report them to your healthcare provider immediately.

Manufacturers are working to increase production capacity as demand for these medications continues to grow but shortages may persist for some time. New approved drugs are on the horizon but it’s important to stay informed and to consult with healthcare professionals for personalized advice. Remember, while compounded medications may offer a solution during shortages, they should be used with caution and careful monitoring by a qualified practitioner.

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